Alcohol withdrawal

Definition

    • Condition that occurs in alcohol abusers as a result of decrease or cessation of alcohol drinking

    • Results in blood alcohol levels below the level to which the drinker has become habituated

    • Begins about 4 to 12 hours after the last drink and may progress to delirium tremens with seizures, hallucinations, coma, and death

Risk Factors

    • Abrupt withdrawal of alcohol

      • The severity of symptoms is proportional to the previous duration and level of alcohol consumed

Differential diagnosis

    • Sympathomimetic intoxication

    • Hepatic encephalopathy

Epidemiology

    • On a worldwide basis, alcohol misuse is responsible for 1.8 million deaths and 58.3 million disability-adjusted life years

    • In 2003, the prevalence of disorders related to alcohol use was 1.7% in developed countries

    • In England, 52,270 hospital admissions in 2005/2006 were directly related to alcohol abuse and there were 6,570 alcohol-related deaths

    • The reporting rate for alcohol-related deaths in the UK is rising, from 6.9 cases per 100,000 in 1991 to 13.4 per 100,000 in 2006

Aetiology

    • Aetiology is not known

    • Chronic alcohol use is associated with:

      • an up-regulation of postsynaptic glutamate receptors

      • or a down-regulation of postsynaptic gamma-amino butyric acid (GABA) receptors

    • Alcohol-related seizures are likely the result of a combination of brain pathology, irritability related to alcohol withdrawal, or trauma related to alcoholism

    • Alcoholic hallucinosis does not have a definitive aetiology; it is known to be related to the severity of dependence and frequency of major withdrawal

Clinical features

    • Alcohol use

      • Structured approach to drinking habits includes asking about alcohol use in the past year and using the CAGE questionnaire to assess whether the patient needs a referral

      • Patients are at risk for major withdrawals if they:

        • drink more than 2 litres of wine or equivalent quantity of hard liquor

        • have a history of heavy alcohol use for more than 5 years

        • usually drink throughout the day

        • have a prior history of withdrawal

    • Change in mental status

      • Patient has severe memory disturbances, remains disoriented to time, place, and person, and has waxing and waning in the level of consciousness

    • Seizures

      • Occurs in 1% to 3% of patients with alcohol withdrawal syndrome

      • Usually happens in the early phase of withdrawal (up to 2 days)

      • Most patients have one seizure that is usually tonic-clonic in nature

      • Focal onset and status epilepticus are rare

    • Hallucinations

      • Examples of visual hallucinations include insects crawling on self or animals circling the bed

      • Tactile hallucinations include sensation of pins or electric shocks all over the body and insects crawling on the skin

      • Associated with delirium tremens (DT), which occurs in 5% of patients hospitalised for alcohol withdrawal

    • Delusions

      • Associated with DT

    • Tremor

      • Associated with minor withdrawal

      • Also a feature of delirium tremens

    • Nausea and vomiting

      • Associated with minor withdrawal

    • Hypertension

      • Associated with minor withdrawal

    • Tachycardia

      • Associated with withdrawal of any severity

    • Fever

      • Associated with major withdrawal and DT

Pathophysiology

    • Prolonged exposure causes adaptive changes in the brain receptors and neurotransmitters

      • Responsible for various effects such as addiction, tolerance, and withdrawal

    • Frequent withdrawal episodes are associated with irreversible brain damage from cell death

      • This phenomenon has been demonstrated in animal studies

    • There are multiple neurotransmitters in the brain that play a role in alcohol withdrawal

      • Their effects are interactive, and some of the neurotransmitters involved include glutamate, GABA, opioid receptors, dopamine, and serotonin receptors

    • One of the excitatory neurotransmitters is glutamate, which acts through the fast-channel NMDA (N-methyl D-aspartate)

      • Alcohol inhibits glutamate, resulting in an increase in the NMDA receptors

      • When an individual stops drinking alcohol, inhibitory effects of alcohol on glutamate stop, and excitatory effects manifest clinically

    • One of the inhibitory chemical substances in the brain is GABA, which acts through the GABA-A receptor

      • It has been shown that increasing the concentration of GABA in the brain produces similar effects to alcohol intoxication

      • It has also been noted in studies that repeated exposure to alcohol can reduce GABA hyperpolarisation and neuronal inhibition, resulting in development of tolerance

    • Dopamine release has been noted in the brain when alcohol is ingested, and alcohol withdrawal is associated with inhibition of dopamine

    • Alcohol use is also associated with an increase in endorphins, and chronic use is associated with lower levels of endorphins

    • Studies show that an increase in serotonin has been noted with alcohol consumption

      • Has shown to be responsible for development of tolerance, intoxication, withdrawal, and regulation of alcohol consumption

    • Increased craving for alcohol after repeated detoxifications is referred to as kindling

      • This occurs as a result of long-term changes in neurons, and explains the progression of withdrawal

Investigations

    • Serum urea and creatinine

      • Elevated, normal, or reduced

      • Dehydration may occur in a delirious patient and may lead to impaired renal function

      • Uraemic encephalopathy can mimic alcohol withdrawal delirium because of change in mental status

    • LFTs

      • All parameters may be elevated

      • May suggest additional diagnoses such as alcoholic hepatitis

    • Toxicology screen

      • May be positive for other drugs of abuse

      • May be used to determine other causes for altered mental status or abnormal vital signs

      • Serum and urine drug testing (both quantitative and qualitative) should be based on clinical suspicion at time of decision making

    • Electrolyte panel

      • Metabolic acidosis

      • Lactic acidosis may be related to alcoholic seizures, ketoacidosis, or ingestion of other alcohols

    • CT head

      • To exclude other causes of the clinical presentation if indicated

Management

a) conservative

    • Supportive care

      • Vitamin supplementation

      • Thiamine supplementation is given if Wernicke’s encephalopathy is suspected

      • Other water-soluble vitamins that may need to be supplemented during hospital or emergency department course include folic acid and magnesium

b) medical

    • benzodiazepine or clomethiazole

      • chlordiazepoxide

        • 25-100 mg orally/intravenously/intramuscularly every 4-6 hours, reduce dose as symptoms abate, maximum 300 mg/day

      • diazepam

        • 5-10 mg orally/intravenously/intramuscularly every 6-8 hours

      • lorazepam

        • 1-4 mg orally/intravenously/intramuscularly every 6-8 hours

    • magnesium

      • Severe hypomagnesaemia (<1 mg/dL) and symptomatic patients in the emergency setting may need up to 2 g of magnesium sulphate given by intravenous infusion

c) surgical

    • n/a

Prognosis

    • Patients may complain of persistent insomnia and autonomic symptoms for a few months after acute withdrawal phase

      • These symptoms usually last about 6 months

    • About 50% of patients remain abstinent for a year

      • Relapse prevention can be achieved by counselling strategies, self-help groups (e.g., Alcoholics Anonymous), and pharmacotherapy