Ethanol Intoxication, Abuse and Dependence

Reviewed and revised 20 May 2016

OVERVIEW

  • Ethanol (ethyl alcohol) is an aliphatic alcohol, C2H5OH
  • The primary effect of ethanol is CNS depression, which is additive with other CNS depressants
  • Ethanol consumption may present as:
    • acute intoxication
    • complication of chronic consumption
    • alcohol withdrawal
    • an underlying or coexistent issue with other disease presentations
  • Alcohol withdrawal syndrome usually develops within 6–24 hours of cessation or reduction in alcohol consumption in dependent individuals. It commonly develops in patients admitted to hospital (see Alcohol withdrawal)
  • Ethanolmay be used therapeutically as an anitdote for toxic alcohol ingestions and for life-threatening alcohol withdrawal

EPIDEMIOLOGY

Ethanol is the most frequently consumed recreational drug in the world

  • >30% of emergency department presentations are alcohol related
  • About 20% of general medical and surgical inpatients will have significant alcohol problems, but will be the reason for admission in about 4%. ~ 8% patients are at risk of alcohol withdrawal
  • males <40 years presenting with trauma are at high risk of withdrawal
  • often an in issue in patients with psychiatric disorder and those taking other recreational drugs
  • often a co-ingestant with other drug overdoses

More harm occurs in the community as a result of the acute health and social effects of alcohol intoxication and abuse than from long-term alcohol dependence

DEFINITIONS

Alcohol abuse

  • Maladaptive pattern of alcohol use leading to clinically significant impairment or distress, manifested within a 12-month period by one or more of the following:
    1. Failure to fulfill role obligations at home, work or school
    2. Recurrent use in hazardous situations
    3. Legal problems related to alcohol
    4. Continued use despite alcohol-related social or inter-personal problems
    5. Symptoms have ever met criteria for alcohol dependence

Alcohol dependence

  • Maladaptive pattern of alcohol use leading to clinically significant impairment or distress, manifested within a 12-month period by three or more of the following:
    1. Tolerance (either increasing amounts or diminished effects with the same amounts)
    2. Withdrawal (withdrawal symptoms or use to relieve or avoid symptoms)
    3. Use of larger amounts over a period longer than intended
    4. Persistent desire or unsuccessful attempts to cut down or control use
    5. Great deal of time spent obtaining or using or recovering from use
    6. Important social, occupational or recreational activities given up or reduced
    7. Use despite knowledge of alcohol-related physical or psychological problems

TOXICODYNAMICS

Ethanol has effects due to activation of numerous receptors:

  • The GABA-A receptor is most important, resulting in Chloride influx into neurons and subsequent inhibitory effects
  • Glycine, N-methyl-D-aspartate, serotonin (5HT3), adenosine and L-type calcium channel effects also appear to be involved

TOXICOKINETICS

Absorption

  • rapid and complete through the gastric mucosa
  • peak levels reached within 30 minutes
  • absorption is delayed by food

Distribution

  • rapid distribution to tissues
  • volume of distribution is 0.6L/kg, equivalent to total body water

Metabolism

  • Ethanol is 90% oxidised by the liver, with the remainder exreted through the kidneys and the lungs (through respiration)
  • Ethanol is metabolized by the cytoplasmic enzyme alcohol dehydrogenase to acetaldehyde (with NADH formation), which is then further oxidized to acetyl CoA/acetic acid by aldehyde dehydrogenase (also with NADH formation)
  • this pathway is saturable, with zero order kinetics supervening above 0.02% (4 mmol/L) concentrations
    • Above this level ethanol is typically metabolised at a rate of 20 mg/dl/h (4 mmol/L/h)
    • Chronic alcohol consumers may metabolise alcohol at a faster rate (see below)
  • The microsomal ethanol oxidizing system (MEOS) is an alternate pathway of ethanol metabolism that occurs in the microsome and results in the oxidation of ethanol to acetaldehyde.
    • minor role in ethanol metabolism in average individuals
    • requires the CYP2E1 enzyme (a cytochrome P450 enzyme) to convert ethanol to acetaldehyde
    • Ethanol’s affinity for CYP2E1 is lower than its affinity for alcohol dehydrogenase
    • MEOS activity increases after chronic alcohol consumption, correlating with an increase in CYP2E1
    • The MEOS pathway oxidises ethanol (losing two hydrogens) and  reduces O2 (by accepting hydrogen) to form H2O. NADPH is used as donor of hydrogen, forming NADP+. This process consumes ATP and dissipates heat resulting in increased resting energy expenditure

SOURCE OF ETHANOL

  • Commercial beverages such as beer, wine, and liquors
  • Colognes, perfumes, after-shaves, mouthwashes, some rubbing alcohols, many food flavorings (eg, vanilla, almond, and lemon extracts), pharmaceutical preparations (eg, elixirs), and other products

CLINICAL FEATURES OF ACUTE INTOXICATION

CNS

  • effects are dependent on blood ethanol level, but varies greatly according to individual variation and tolerance
    • chronic high ethanol consumers appear less intoxicated at higher blood concentrations – they may even appear sober at levels that would serious affect alcohol naive patients
    • females tend to have less tolerance than males
  • typical
    • <50 mg/dL: may be asymptomatic
    • 50-100 mg/dL: relaxation, sedation, prolonged reaction time,euphoria
    • 100-200 mg/dL: impaired motor function and coordination, dysarthria, ataxia
    • 200-300 mg/dL: emesis, stupor
    • 300-400 mg/dL: coma
    • >500 mg/dL: respiratory depression, death
  • time course
    • Improvement in conscious state is usually seen with 2-4 hours
    • Patients may not be normally ambulant for 6-12 hours

Other organ systems

  • CVS: myocardial depression at high doses; systemic vasodilation
  • RENAL: diuresis (due to inhibition of ADH secretion)
  • GI: gastritis, hepatitis, acute pancreatitis
  • RESP: aspiration
  • METABOLIC: hypoglycaemia, hyperlactaemia (NADH production from ethanol metabolism impairs gluconeogenesis and fatty acid beta-oxidation as well as conversion of lactate to pyruvate)
  • MSKEL: rhabdomyolysis (from immobility)

Have a high suspicion of occult trauma (e.g. head injury) in the patient with acute ethanol intoxication

INVESTIGATIONS

Bedside

  • Breathalyser (quantitative measured of breath alcohol level)
  • ECG (cardiomyopathy)
  • BSL (hypoglyceamia)
  • blood gas (hyperlactaemia)
  • ketones (alcoholic ketoacidosis – tends to occur in poorly nourished chronic alcohol consumers a few days after a binge, rather than during acute intoxication)

Laboratory

  • ethanol level (does not exclude co-existant causes of altered mental state)
  • high osmolar gap (severe acute intoxication)
  • LFTs, lipase (if abdominal pain)
  • paracetamol level (if suspected self harm)
  • abnormalities proportional to severity of chronic use:
    • hyponatraemia
    • hypokalaemia
    • hypomagnesaemia
    • hypophosphataemia
    • hypoglycaemia (especially if malnoursihed with depleted glycogen stores)
    • hypertriglyeridaemia
    • leukopaenia
    • thrombocytopaenia
    • coagulopathy
    • macrocytic anaemia (due to aloohol)
    • microcytic anaemia (if chronic blood loss)

Imaging

  • CT Brain: low threshold for CT brain if suspected trauma or failure of altered mental state to improve over 2-4 hours

MANAGEMENT OF ACUTE ETHANOL INTOXICATION

Resuscitation

  • seek and treat life threats
    • airway compromise from decreased level of consciousness
      • airway opening manoeuvres and adjuncts, suction, close observation
      • intubation may be required
    • ventilatory support if respiratory depression or aspiration
    • hypoglycaemia (due to severe ethanol intoxication)
    • coexistent life-threats (e.g. GI haemorrhage, trauma)

Supportive care and monitoring

  • thiamine 300mg IV
  • adequate hydration
  • replace electrolytes and vitamins
  • manage behavioural disturbance (verbal de-escalation, chemical +/- physical restraint if indicated)
  • commence an alcohol withdrawal chart

Seek and treat underlying causes and complications

  • consider coexistent disorders (e.g. occult head injury, coingestion)
  • screen for chronic alcohol problems and complications

Disposition

  • Acute uncomplicated alcohol intoxicated patients may be observed in the ED till more fully awake and are able to make decisions about their own welfare and ensure their own safety.
  • Patients who are incompetent to make decisions about their own welfare must not be discharged. Physical restraint, even some chemical restraint may sometimes be required to keep the patient safe.
  • Acutely intoxicated patients should usually be observed in the emergency department until BAC reaches 0.2 g%
  • Drivers involved in motor vehicle accidents that are suspected of intoxication or who have not breathalyzed at zero, will require police blood alcohol samples to be taken.
  • Withdrawal
    • may begin at a BAL of 0.1 g% and will usually have begun before the concentration reaches zero
  • Admission may be required for:
    • social crisis (poor supervision or support)
    • medical (high risk of withdrawal, suspected coexistent illness or complication of chronic alcohol consumption)
  • Referrals, when appropriate to:
    • Emergency accommodation
    • Social worker/ support services
    • Drug and Alcohol service
    • Child welfare services (if suspect NAI or children at risk)

CHRONIC ALCOHOL DEPENDENCE

Levels considered damaging in the long term (taken daily for 5 years or more) are:

  • Males: 60 g/day
  • Females: >40 g/day

The potential complications of chronic alcohol consumption are extensive:

  • GENERAL: abdo pain, weight loss, poor nutrition, recurrent falls, relationship breakdowns and social isolation
  • HEPATIC:  fatty infiltration and alcoholic hepatitis, cirrhosis, jaundice, hypoglycaemia, ascities, hepatic encephalopathy
  • CVS: dilated cardiomyopathy, hypertension
  • NEURO: Wernicke-Korsakoff syndrome, dementia, depression, peripheral neuropathy, cerebellar degeneration, Marchiafava-Bignami syndrome (cortical necrosis), seizures; alcohol withdrawal
  • GI: varices, portal hypertension,gastritis, GI haemorrhage, pancreatitis
  • METABOLIC: mineral and electrolyte deficiencies, hypothermia
  • HAEM: thrombocytopaenia, coagulopathy; haemorrhage (e.g. intra-cranial)
  • FETUS: fetal alcohol syndrome
  • NEOPLASM: oral, throat, esophageal, gastric, hepatic cancers

SCREENING AND BRIEF INTERVENTIONS FOR ALCOHOL PROBLEMS

Screening tools include:

  • CAGE questions
    • detects alcohol abuse and dependence
    • sensitivity 43–94%, specificity 70–97%
    • Two or more positive responses identify patients with lifetime risk of alcohol problems
      • Cut down: Have you ever tried to cut down your drinking?
      • Annoyed: Have you ever been annoyed by criticism of your drinking?
      • Guilty: Do you feel guilty about your drinking?
      • Eye-opener: Do you need an eye-opener when you get up on the morning?
  • Alcohol Use Disorders Identification Test (AUDIT)
    • identifies patients with at-risk, hazardous or harmful drinking
    • sensitivity 51–97%, specificity of 78–96%
  • This single question when administered to trauma patients, using a cut-off of three drinks, correlates with the AUDIT score: ʻOn a typical day when you are drinking, how many drinks do you have?ʼ

The ‘FRAMES’ approach is a useful brief intervention for decreasing alcohol consumption in non-dependent patients:

  • Feedback: review problems caused by alcohol with the patient
  • Responsibility: point out that changing behaviour is the patient’s responsibility
  • Advice: advise the patient to cut down or abstain from alcohol
  • Menu: provide options to assist the patient change behaviour
    Empathy: use an empathetic approach
  • Empathy: use an empathetic approach
  • Self-efficacy: encourage optimism that the patient can change behaviour

OTHER INFORMATION

Legal blood alcohol limit for driving

  • 0.05% in the state of Victoria
  • may differ in other parts of the world

Unit conversion

  • To convert SI units to mg/dL multiply by 4.61
  • To convert mg/dL to SI units multiply by 0.22

Content of alcoholic beverages

Type% by volumeVolume containing 10 g alcohol
Low Alcohol Beer2-3%425 mL (15 oz)
Ordinary Beer4-5%285 mL (10 oz)
Table Wine10%120 mL (4 oz)
Fortified Wine20%60 mL (2 oz)
Spirits (nip)40%30 mL (1 oz)

References and Links

LITFL

Journal articles

  • Friedmann PD. Clinical practice. Alcohol use in adults. The New England journal of medicine. 368(4):365-73. 2013. [pubmed]
  • Mehta AJ. Alcoholism and critical illness: A review. World journal of critical care medicine. 5(1):27-35. 2016. [pubmed] [free full text]

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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