Alcohol withdrawal overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2] Aditya Govindavarjhulla, M.B.B.S. [3]
Overview
Alcohol withdrawal occurs with sudden discontinuation of alcohol intake after consumption of large quantities of alcohol for more than two weeks. The incidence of alcohol dependence is approximately 8 million individuals, annually, in the United States, and about 50% of them experience alcohol withdrawal symptoms with decreased or discontinuation of alcohol consumption. Common symptoms of alcohol withdrawal may include loss of appetite, nausea, vomiting, agitation, anxiety, irritability, insomnia, headache, diaphoresis, tremor, and the most severe symptoms in alcohol withdrawal include hallucinosis, seizures, and delirium tremens (DT). Symptoms of alcohol withdrawal usually resolve within seven days of alcohol intake discontinuation. Most patients with alcohol withdrawal have mild symptoms and may be treated with outpatient management. 5% of patients with alcohol withdrawal will present with severe alcohol withdrawal characteristics including seizures and delirium tremens (DT). The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria is used to diagnose alcohol withdrawal. The Clinical Institute Withdrawal Assessment for Alcohol (CIWA-A) scale is used to assess the severity of alcohol withdrawal. Benzodiazepines are currently the gold standard treatment of alcohol withdrawal such as diazepam, chlordiazepoxide, lorazepam, and oxazepam. Other drugs that may be used are phenobarbital, propofol, and dexmedetomidine. Thiamine is usually administered for prevention of Wernicke encephalopathy (prior to glucose administration).
Historical Perspective
The term 'alcoholism' was first used in medical texts by Magnus Huss in 1894.[1]
Classification
Stages of Alcohol Withdrawal Syndrome (AWS) may be classified as:[2]
- Uncomplicated withdrawal (first 6 hours)
- Alcohol hallucinosis (8-12 hours)
- Alcohol withdrawal seizures (12-24 hours)
- Alcohol withdrawal delirium (24-72 hours)
Pathophysiology
Under normal conditions in the brain, there is a balance between excitatory neurotransmitters such as glutamate and inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA).[3]
Chronic alcohol intake and acute discontinuation of alcohol intake affect the balance of the neurotransmitters and cause many of the symptoms observed in alcohol withdrawal.[4] [5][2][3]
Acute Alcohol Consumption
- Increases the GABA neurotransmitter and sensitivity of GABA-A receptor subtypes, which in turn, increases inhibitory neurotransmission.
- Prevents the effects of glutamate (an excitatory neurotransmitter) on the N-methyl-d-aspartate (NMDA) receptors by inhibiting the binding of glycine to the NMDA receptors.[6][7]
Chronic Alcohol Consumption
- Causes tolerance and compensation by downregulation GABA-A receptors and upregulating NMDA receptors, and requires higher blood levels of alcohol to cause the same effect.[6][7]
Alcohol Withdrawal in Chronic Alcohol Consumption
- Exposes the downregulation of GABA-A receptors and the upregulation of NMDA receptors, resulting in hyperexcitability of the neurons that lower the threshold for seizures.[4][8][9]
- Upregulation of noradrenergic and dopaminergic receptors cause the autonomic hyperactivity and hallucinations that are seen in patients with alcohol withdrawal.[10]
- Kindling is increased excitability and sensitivity of the neurons after repeated events of alcohol withdrawal,[11][12] and is suggested to be the reason for progressing from milder to more severe symptoms of alcohol withdrawal in some patients.[4]
Causes
Alcohol withdrawal occurs with sudden discontinuation of alcohol intake after consumption of large quantities of alcohol for more than two weeks.[13]
Differentiating Alcohol Withdrawal from Other Diseases
Alcohol withdrawal must also be differentiated from other diseases including:[14]
- Diabetic ketoacidosis
- Essential tremor
- Hypoglycemia
- Sedative, hypnotic, or anxiolytic withdrawal
Epidemiology and Demographics
- The incidence of alcohol dependence is approximately 8 million individuals, annually, in the United States, and about 50% of them experience alcohol withdrawal symptoms with decreased or discontinuation of alcohol consumption.[15][14]
- The prevalence of alcohol withdrawal is approximately 50% of middle-class individuals with alcohol use disorder.
- The prevalence of alcohol withdrawal is approximately 80% of hospitalized or homeless individuals with alcohol use disorder.[14]
- 5% of patients with alcohol withdrawal will present with severe alcohol withdrawal symptoms including seizures and delirium tremens (DT).[16] 5% of patients with alcohol withdrawal and delirium tremens (DT) die from various complications such as cardiovascular, metabolic, infections, and trauma.[17][18]
- Alcohol withdrawal is rare in patients <30 years old, and the severity increases with more age.[14]
- It is estimated that about 20% of men and 10% of women have alcohol use disorder, and in about half of them alcohol withdrawal symptoms will be observed with a decrease in alcohol intake.[15][14]
Risk Factors
Risk factors for alcohol withdrawal include:[14]
- Quantity and frequency of alcohol consumption
- Family history of alcohol withdrawal
- Prior withdrawals
- Sedative, hypnotic, or anxiolytic drugs
Natural History, Complications, and Prognosis
- Symptoms of alcohol withdrawal usually resolve within seven days of alcohol intake discontinuation.[13]
- Most patients with alcohol withdrawal have mild symptoms and may be treated with outpatient management.[16]
- 5% of patients with alcohol withdrawal will present with severe alcohol withdrawal characteristics including seizures and delirium tremens (DT).[16]
- 5% of patients with alcohol withdrawal and delirium tremens (DT) die from complications such as cardiovascular, metabolic, infections, and trauma.[17][18]
Diagnosis
Diagnostic Criteria
- The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria is used to diagnose alcohol withdrawal.[14]
- The Clinical Institute Withdrawal Assessment for Alcohol (CIWA-A) scale is used to assess the severity of alcohol withdrawal.[19]
History and Symptoms
The most common symptoms of alcohol withdrawal include:[3]
- Loss of appetite, anorexia
- Craving for alcohol
- Nausea, vomiting
- Agitation
- Anxiety
- Irritability
- Hypervigilance
- Insomnia
- Vivid dreams
- Headache
- Diaphoresis
- Tremor
The most severe symptoms in alcohol withdrawal include [3]
Physical Examination
Signs to consider in the physical examination of patients with alcohol withdrawal may include:[2]
- Anxiety
- Nausea, vomiting
- Tremors
- Autonomic hyperactivity (tachycardia, hypertension, and hyperthermia)
- Hallucinations (auditory, visual, tactile, gustatory, and olfactory)
- Delusions
- Confusion
- Seizure
- Delirium tremens (DT)
Laboratory Findings
Routine laboratory tests should include:[4]
- Blood or breath alcohol concentration
- Complete blood count (CBC)
- Electrolytes
- Glucose
- Liver function tests
- Renal function tests
- Urinalysis
- Urine toxicology
CT scan
- There are no CT scan findings associated with alcohol withdrawal.
- However, it has been suggested that in linear CT scan measurements in patients that are dependent on alcohol and have a history of delirium tremens, the maximum width of the anterior interhemispheric fissure (MIF) and the maximum width of the Sylvian fissure (MSF) are significantly larger compared to those patients that did not have delirium tremens and controls.[20]
Other Imaging Findings
- There are no MRI findings associated with alcohol withdrawal.
- Studies have suggested a decrease in hippocampal volume on a MRI may represent brain atrophy in patients with chronic alcoholism, however, a decrease in hippocampal volume has been suggested to have no association with seizures during alcohol withdrawal.[21]
Other Diagnostic Studies
- There are no other diagnostic studies associated with alcohol withdrawal.
- However, studies with neurochemical brain imaging [with magnetic resonance spectrometry (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT)] have shown the neurochemical (GABA, glutamate, and dopamine) effects during alcohol dependence and withdrawal such as:[22]
Treatment
Medical Therapy
The medical management of alcohol withdrawal includes:[5][4]
- Supportive and nonpharmacological therapy:
- Airway protection
- Monitoring of vital signs
- Assessment of adequate hydration
- Vitamin and electrolyte replacement:
- Thiamine for prevention of Wernicke encephalopathy (prior to glucose administration)
- Folate supplementation
- Electrolyte imbalances may be seen in alcohol withdrawal due to inadequate nutrition and hydration:
- Hypokalemia (may be corrected with potassium supplementation)
- Hypomagnesemia (routine supplementation of magnesium is not recommended)
- Hypophosphatemia (in asymptomatic and moderate hypophosphatemia, correction with proper nutrition is preferred)
- Benzodiazepines (currently the gold standard treatment of alcohol withdrawal): diazepam, chlordiazepoxide, lorazepam, and oxazepam
- Phenobarbital
- Propofol (an agonist at the GABA-A receptor)
- Dexmedetomidine (α-2 adrenergic receptor agonist)
Surgery
Surgical intervention is not recommended for the management of alcohol withdrawal.
Primary Prevention
Refraining from sudden and abrupt discontinuation of alcohol intake in individuals with alcohol dependence may be considered in the primary prevention of alcohol withdrawal.
Secondary Prevention
Long-term abstinence may be considered in the secondary prevention of alcohol withdrawal. Abstinence requires enrollment in long-term treatment programs in order to reduce the risk of relapse, such as:[23][13]
- Group meetings
- Counseling
- Medications
Cost-Effectiveness of Therapy
- Outpatient detoxification and treatment are more cost-effective in patients with mid-to-moderate alcohol withdrawal symptoms. [24]
- Outpatient treatment costs are about $175 to $388 per patient.
- Inpatient treatment costs are about $3,319 to $3,665 per patient.
Future or Investigational Therapies
Further studies are required for:[3][25]
- Investigating the exact molecular and genetic mechanisms that cause the different symptoms of withdrawal
- Kindling and the risk factors that cause severe withdrawal
- The most appropriate treatment
- Methods that help the patients in relapse prevention
- Methods that improve the physician recognition of alcohol dependence
- Methods that improve receiving evidence-based treatment
References
- ↑ Lesch OM, Dietzel M, Musalek M, Walter H, Zeiler K (1988). "The course of alcoholism. Long-term prognosis in different types". Forensic Sci Int. 36 (1–2): 121–38. doi:10.1016/0379-0738(88)90225-3. PMID 3338683.
- ↑ 2.0 2.1 2.2 Wolf C, Curry A, Nacht J, Simpson SA (2020). "Management of Alcohol Withdrawal in the Emergency Department: Current Perspectives". Open Access Emerg Med. 12: 53–65. doi:10.2147/OAEM.S235288. PMC 7093658 Check
|pmc=value (help). PMID 32256131 Check|pmid=value (help). - ↑ 3.0 3.1 3.2 3.3 3.4 Saitz R (1998). "Introduction to alcohol withdrawal". Alcohol Health Res World. 22 (1): 5–12. PMC 6761824 Check
|pmc=value (help). PMID 15706727. - ↑ 4.0 4.1 4.2 4.3 4.4 Mirijello A, D'Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F; et al. (2015). "Identification and management of alcohol withdrawal syndrome". Drugs. 75 (4): 353–65. doi:10.1007/s40265-015-0358-1. PMC 4978420. PMID 25666543.
- ↑ 5.0 5.1 Schmidt KJ, Doshi MR, Holzhausen JM, Natavio A, Cadiz M, Winegardner JE (2016). "Treatment of Severe Alcohol Withdrawal". Ann Pharmacother. 50 (5): 389–401. doi:10.1177/1060028016629161. PMID 26861990.
- ↑ 6.0 6.1 Goodman, Louis (2011). Goodman & Gilman's pharmacological basis of therapeutics. New York: McGraw-Hill. ISBN 978-0-07-162442-8. OCLC 498979404.
- ↑ 7.0 7.1 Nelson, Lewis (2011). Goldfrank's toxicologic emergencies. New York: McGraw-Hill Medical. ISBN 978-0-07-160594-6. OCLC 470694511.
- ↑ Kosten TR, O'Connor PG (2003). "Management of drug and alcohol withdrawal". N Engl J Med. 348 (18): 1786–95. doi:10.1056/NEJMra020617. PMID 12724485.
- ↑ Hall W, Zador D (1997). "The alcohol withdrawal syndrome". Lancet. 349 (9069): 1897–900. doi:10.1016/S0140-6736(97)04572-8. PMID 9217770.
- ↑ McKeon A, Frye MA, Delanty N (2008). "The alcohol withdrawal syndrome". J Neurol Neurosurg Psychiatry. 79 (8): 854–62. doi:10.1136/jnnp.2007.128322. PMID 17986499.
- ↑ Lejoyeux M, Solomon J, Adès J (1998). "Benzodiazepine treatment for alcohol-dependent patients". Alcohol Alcohol. 33 (6): 563–75. doi:10.1093/alcalc/33.6.563. PMID 9872344.
- ↑ Reoux JP, Saxon AJ, Malte CA, Baer JS, Sloan KL (2001). "Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo-controlled clinical trial". Alcohol Clin Exp Res. 25 (9): 1324–9. PMID 11584152.
- ↑ 13.0 13.1 13.2 Muncie HL, Yasinian Y, Oge' L (2013). "Outpatient management of alcohol withdrawal syndrome". Am Fam Physician. 88 (9): 589–95. PMID 24364635.
- ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN 0890425558.
- ↑ 15.0 15.1 Schuckit MA (2009). "Alcohol-use disorders". Lancet. 373 (9662): 492–501. doi:10.1016/S0140-6736(09)60009-X. PMID 19168210.
- ↑ 16.0 16.1 16.2 Schuckit MA (2014). "Recognition and management of withdrawal delirium (delirium tremens)". N Engl J Med. 371 (22): 2109–13. doi:10.1056/NEJMra1407298. PMID 25427113.
- ↑ 17.0 17.1 VICTOR M, ADAMS RD (1953). "The effect of alcohol on the nervous system". Res Publ Assoc Res Nerv Ment Dis. 32: 526–73. PMID 13134661.
- ↑ 18.0 18.1 Cutshall BJ (1965). "The Saunderssutton syndrome: an analysis of delirium tremens". Q J Stud Alcohol. 26 (3): 423–48. PMID 5858249.
- ↑ Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM (1989). "Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar)". Br J Addict. 84 (11): 1353–7. doi:10.1111/j.1360-0443.1989.tb00737.x. PMID 2597811.
- ↑ Maes M, Vandoolaeghe E, Degroote J, Altamura C, Roels C, Hermans P (2000). "Linear CT-scan measurements in alcohol-dependent patients with and without delirium tremens". Alcohol. 20 (2): 117–23. doi:10.1016/s0741-8329(99)00066-x. PMID 10719790.
- ↑ Bleich S, Sperling W, Degner D, Graesel E, Bleich K, Wilhelm J; et al. (2003). "Lack of association between hippocampal volume reduction and first-onset alcohol withdrawal seizure. A volumetric MRI study". Alcohol Alcohol. 38 (1): 40–4. doi:10.1093/alcalc/agg017. PMID 12554606.
- ↑ Hillmer AT, Mason GF, Fucito LM, O'Malley SS, Cosgrove KP (2015). "How Imaging Glutamate, γ-Aminobutyric Acid, and Dopamine Can Inform the Clinical Treatment of Alcohol Dependence and Withdrawal". Alcohol Clin Exp Res. 39 (12): 2268–82. doi:10.1111/acer.12893. PMC 4712074. PMID 26510169.
- ↑ Blondell RD (2005). "Ambulatory detoxification of patients with alcohol dependence". Am Fam Physician. 71 (3): 495–502. PMID 15712624.
- ↑ Hayashida M, Alterman AI, McLellan AT, O'Brien CP, Purtill JJ, Volpicelli JR, Raphaelson AH, Hall CP (1989). "Comparative effectiveness and costs of inpatient and outpatient detoxification of patients with mild-to-moderate alcohol withdrawal syndrome". The New England Journal of Medicine. 320 (6): 358–65. doi:10.1056/NEJM198902093200605. PMID 2913493. Retrieved 2012-08-16. Unknown parameter
|month=ignored (help) - ↑ Fiellin DA, Samet JH, O'Connor PG (1998). "Reducing Bias in Observational Research on Alcohol Withdrawal Syndrome". Subst Abus. 19 (1): 23–31. doi:10.1080/08897079809511370. PMID 12511804.