Alcohol withdrawal

Alcohol withdrawal syndrome (AWS) refers to the excitatory state that develops after a sudden cessation of or reduction in alcohol consumption following a period of prolonged heavy drinking. It is characterized by a variety of clinical features, including tremor, insomnia, anxiety, and autonomic instability. AWS is considered to be complicated if patients present with or develop alcohol withdrawal seizures, alcohol withdrawal delirium, or alcohol-induced psychotic disorder. AWS is a clinical diagnosis of exclusion based on characteristic symptoms in at-risk patients with recent reduction or cessation of alcohol consumption. Patients with AWS may also present with concomitant diseases that require treatment (e.g., alcoholic hepatitis, complicated cirrhosis) or develop AWS during periods of hospitalization for unrelated comorbidities. The management of uncomplicated and complicated AWS includes hydration, nutritional support, and thiamine to prevent or treat concomitant Wernicke encephalopathy, as well as pharmacological management with benzodiazepines and/or anticonvulsants to reduce symptoms and prevent disease progression and death. Most patients require hospital admission for monitoring and treatment.

A transient excitatory state caused by a sudden cessation of or reduction in alcohol consumption after a prolonged period of heavy drinking

References ^[1][2]

AWS is typically described as the progression through the stages of alcohol withdrawal, from minor to severe withdrawal with or without complicated disease. Not all patients progress through all of the stages of AWS, especially elderly patients and/or patients taking hypnotic or anxiolytic medications.

Alcohol withdrawal syndrome (uncomplicated) ^[2][3]

• Onset: : usually 6–24 hours after cessation of or reduction in alcohol consumption ^[2]
• Clinical features: can appear on a spectrum of severity from mild to severe (see “Classification”)
  • Autonomic symptoms (e.g., palpitations, sweating, tachycardia, elevated blood pressure, hyperthermia)
  • Anxiety, insomnia, vivid dreams
  • Tremor, hyperreflexia
  • Headaches
  • Anorexia, nausea, vomiting

Alcohol withdrawal seizures ^[2][3]

• Onset: : usually 8–48 hours after cessation of or reduction in alcohol consumption ^[2]
• Clinical features
  • Usually brief, generalized tonic-clonic seizures
  • Often a single episode

Withdrawal seizures may occur without prior significant features of AWS and may be the presenting symptom in some patients.

Alcohol-induced psychotic disorder (alcoholic hallucinosis) ^[2][3]

• Onset: : usually 12–24 hours after cessation of or reduction in alcohol consumption ^[2]
• Clinical features
  • Consciousness is usually intact.
  • Vital signs may be normal.
  • Auditory and/or visual hallucinations are common; (tactile hallucinations are also possible).
  • Delusions
• Duration: 24–48 hours after onset ^[2]

It may be challenging to distinguish alcoholic hallucinosis from the hallucinations associated with delirium; patients with delirium usually have impaired consciousness and abnormal vital signs.

Alcohol withdrawal delirium (delirium tremens) ^[2][3]

• Definition: : persistent alteration of consciousness and sympathetic hyperactivity due to alcohol withdrawal
• Onset: usually 72–96 hours after cessation of or reduction in alcohol consumption
• Clinical features
  • Symptoms of altered mental status
    • Impaired consciousness and disorientation
    • Visual and tactile hallucinations (usually small moving objects, e.g., mice, crawling insects), oneirism (a condition characterized by visual hallucinations, typically experienced during a waking state, that are dreamlike and rich in detail)
    • Increased suggestibility
  • Worsening symptoms of autonomic instability
    • Tachycardia
    • Hypertension
    • Anxiety
    • Nausea
    • Sweating
  • Worsening symptoms of neurological impairment
    • Psychomotor agitation (e.g., fidgeting, restlessness, tearfulness)
    • Alcohol withdrawal seizures can occur during this phase.
    • Insomnia
    • Rest and intention tremor (first high frequency, then low frequency)
• Duration: : usually 2–3 days; may be lethal

Classification by syndrome ^[1][2]

• Complicated alcohol withdrawal refers to AWS with any of the following:
  • Alcohol withdrawal seizures
  • Alcohol withdrawal delirium
  • Alcohol-induced psychotic disorder
• Resistant alcohol withdrawal: severe symptoms of AWS or the presence of complications despite the use of high benzodiazepine doses ^[2]

Classification by severity ^[4]

CIWA-Ar is the most common tool used to assess and classify alcohol withdrawal severity into the following categories: absent, mild, moderate, and severe.

The CIWA-Ar is a useful tool to assess alcohol withdrawal severity that can help guide management and prevent complications in patients diagnosed with AWS.

Approach ^[2][3]

• Clinical diagnosis: Suspect AWS in patients with characteristic clinical features and a history of alcohol use disorder who have recently ceased or reduced their alcohol consumption (use the “DSM-5 criteria for AWS”).
• Complicated AWS should be considered if any of the following are present:
  • Alcohol-induced psychotic disorder: Consultation with a psychiatrist is advised for a workup of psychotic disorders.
  • Alcohol withdrawal delirium: Patients should also fulfill the DSM-5 diagnostic criteria for delirium.
  • Alcohol withdrawal seizures: Perform a diagnostic workup of seizure disorders.
• Additional investigations
  • Order routine diagnostic studies and blood alcohol concentration.
  • Consider additional investigations based on suspected comorbidities and differential diagnoses for substance intoxication.
  • Screen for depressive disorder and suicidal ideation.

Patients with AWS often have other disorders that also require urgent identification and treatment (e.g., alcoholic hepatitis, sepsis, traumatic brain injury, Wernicke encephalopathy, decompensated liver cirrhosis).

Individuals with chronic alcohol use who are hospitalized often develop withdrawal symptoms 48–72 hours after admission because they do not have access to alcohol in the hospital. Consider screening admitted patients for alcohol use disorder using a validated tool (e.g., CAGE or AUDIT-C test).

Clinical diagnostic criteria ^[6]

Additional investigations ^[2]

• Routine laboratory studies: Laboratory alterations detected in patients with AWS are often attributable to chronic alcohol use disorder.
  • CBC
  • BMP
  • Extended electrolytes: e.g., calcium, magnesium, phosphate
  • Liver chemistries
  • Other markers of liver function: e.g., INR, albumin
  • Amylase, lipase
  • Blood gas analysis
• Blood alcohol concentration (BAC): Symptoms that occur while BAC is still detectable or high carry a poor prognosis for progression to severe AWS.
• Other tests to consider ^[7]
  • Toxicological screening for suspected co-ingested substances.
  • Septic workup
  • Delirium workup
  • Neuroimaging
  • HIV and hepatitis screening.
  • PHQ-2 and modified SAD PERSONS scale

Laboratory findings in AWS are usually attributable to chronic alcohol use disorder and tend to be mild. Marked alterations should prompt suspicion for comorbid conditions.

Approach ^[2][8]

• Anticipate and prevent alcohol withdrawal in at-risk patients hospitalized for other reasons.
• Classify AWS severity using a validated scale, e.g., CIWA-Ar.
• Perform risk assessment for AWS (to predict severe or complicated AWS): e.g., identify red flags for alcohol withdrawal and/or calculate PAWSS score.
• Adjust pharmacotherapy and disposition according to individual symptom severity and risk of progression (see “Management algorithm for AWS”).
• Consider using severity scale (e.g., CIWA-Ar) to monitor response to treatment.
• Identify and manage any complications without delay (see “Management of complicated AWS”).
  • Alcohol withdrawal seizures: Immediately administer IV benzodiazepines.
  • Alcohol-induced psychotic disorder: Consider ; low-dose antipsychotics (e.g., haloperidol; , risperidone) in combination with benzodiazepines (not as monotherapy).
  • Alcohol withdrawal delirium: Consider referral to critical care unit for high-dose IV benzodiazepines and monitoring.
• Provide supportive care to all patients during the withdrawal episode (e.g., nutritional and metabolic support).
• Offer treatment of alcohol use disorder.
  • Consider brief interventional counseling on alcohol use disorder during hospitalization.
  • Provide referral for long-term therapy if the patient is interested.

In the event of alcohol withdrawal seizures, benzodiazepines are preferred over other anticonvulsants to prevent further seizures.

Pharmacotherapy

See “Pharmacological treatment regimens for AWS” for detailed recommendations and dosages.

• First-line: benzodiazepines
  • Shorter or intermediate-acting (e.g., oxazepam, lorazepam): Consider in patients with a slow metabolism (e.g., the elderly, those with liver failure).
  • Longer acting (e.g., chlordiazepoxide, diazepam): preferred in all other patients
• Second-line: Anticonvulsants can be used in AWS if there are contraindications for benzodiazepines or as adjunctive treatment in resistant AWS.

Lorazepam, Oxazepam, and Temazepam are preferred for individuals who drink a LOT (have alcoholic liver disease), because hepatic dysfunction does not have a strong effect on their metabolism. ^[9]Lorazepam, Oxazepam, and Temazepam are preferred for individuals who drink a LOT (have alcoholic liver disease), because hepatic dysfunction does not have a strong effect on their metabolism. All benzodiazepines are metabolized by the liver, but these three undergo biotransformation through glucuronidation, not CYP 450 activation, and are less affected by liver disease. ^[9]

Supportive care ^[2]

• Hydration: : Provide IV fluid therapy as needed and start fluid balance monitoring.
• Metabolic support: Assess nutritional status and need for vitamin and mineral replacement.
  • Consider multivitamins.
  • Provide folate for critically ill patients. ^[2]
  • Electrolyte repletion: e.g., for hypokalemia, hyponatremia, or hypomagnesemia
  • Treatment of hypoglycemia: oral glucose or IV 50% dextrose (see also “Alcoholic ketoacidosis”)
  • Thiamine supplementation
    • Patients with Wernicke encephalopathy: therapeutic-dose thiamine
    • All other patients: prophylactic-dose thiamine
  • Fixed-dose combined vitamin and mineral replacement (i.e., the “banana bag” approach): no longer recommended as part of routine management; ^[2][10]
• Comorbidites: Treat any identified coexisting illnesses, e.g., toxic co-ingestions, GI bleeding, sepsis, alcoholic hepatitis, pancreatitis, injuries, depression, suicidality

Do not delay glucose administration when indicated; evidence suggests that it is safe to administer glucose without prior thiamine supplementation. ^[2][11]

Risk assessment for alcohol withdrawal

Multifactorial risk assessment is recommended for patients on an individual basis.

Red flags for alcohol withdrawal ^[2][8]

The more red flags identified, the higher the risk of progression to severe or complicated AWS and failure of outpatient management. ^[2]

• Patient characteristics
  • Age > 65 years
  • Significant medical comorbidities
  • Significant psychiatric comorbidities: e.g., active risk of suicide, psychosis.
  • Chronic, heavy drinking: e.g., positive AUDIT-C or CAGE
  • Low social supports and/or unsafe living environment
• Related to the current withdrawal episode
  • Severe AWS: e.g. significant autonomic hyperactivity
  • Complicated AWS: e.g., seizures during the current withdrawal episode
  • Presence of AWS symptoms with detectable BAC
  • Additional acute illness
  • Significant abnormal laboratory results (see “Diagnostics”)
  • Simultaneous withdrawal from other substances or significant use of or dependence on other drugs
• Related to previous withdrawal episodes
  • Multiple prior AWS episodes
  • History of complicated AWS

Validated risk scores ^[12][13]

Different risk scores are used in clinical practice due to varying advantages and limitations. ^[14][15]

• CIWA-Ar: higher value as a severity score than a risk score.
  • Clinical applications
    • Establishing baseline severity
    • Monitoring of progression
    • Evaluating response to treatment
  • Limitations
    • Subjectivity in assessment parameters
    • Difficult to apply to uncommunicative or uncooperative patients
    • Less predictive of the risk of severe AWS, complicated AWS, or future withdrawal.
• PAWSS score: greater predictive value to identify hospitalized patients at risk of complicated AWS ^[13]

Management algorithm ^[2][8]

Most patients require inpatient management.

Monitor for signs of oversedation in all patients with AWS receiving pharmacological therapy.

Outpatient management of patients with moderate or severe alcohol withdrawal without red flags for AWS should only be considered if specialized centers and facilities for ambulatory monitoring are available, or if management can be provided by an experienced clinician. ^[2][8]

Management of complicated AWS ^[2]

Complications can occur at any point during withdrawal (e.g., upon presentation) and often necessitate escalation of the level of care (e.g., specialist or critical care consultation and high-dose pharmacotherapy). Follow local protocols if available.

• Alcohol withdrawal seizures: Rapid administration of parenteral fast-acting benzodiazepines: e.g., diazepam
  • Continue monitoring every 1–2 hours for 6–24 hours.
  • If there is no response to benzodiazepines, administer anticonvulsants for AWS.
• Alcohol-induced psychotic disorder: consider combination therapy in consultation with a specialist
  • Benzodiazepines: Consider a front-loading dose for AWS to reduce symptoms.
  • Adjunct: consider adding antipsychotics (e.g., haloperidol, risperidone)
• Alcohol withdrawal delirium ^[18]
  • High-dose benzodiazepines: Administer a front-loading dose for AWS until mild sedation is achieved.
  • Monitor delirium symptoms frequently using the “Confusion assessment method.”
  • See “Treatment of agitation in delirium” for additional recommendations.
• Next steps
  • After acute symptoms resolve, continue a pharmacological fixed-schedule regimen for AWS to prevent recurrences.
  • Consider ICU admission and specialist consultation.

These patients often require large doses of benzodiazepines, increasing the risk of oversedation and respiratory depression. Ensure that resuscitative equipment is readily available (e.g., bag-mask ventilation, supplemental O₂, advanced airway devices).

• Choose the most suitable pharmacological regimen based on the management algorithm for AWS. ^[2]
• Discontinue benzodiazepines as soon as AWS is resolved to reduce the potential for dependence. ^[2]

Hepatic impairment can cause the accumulation of benzodiazepines and their active metabolites. Consider preferentially using lorazepam, oxazepam, or temazepam in patients with liver disease to reduce the risk of oversedation. ^[19][20]

As a rule of thumb, the following doses of benzodiazepines are considered roughly equivalent in patients with normal hepatic function: diazepam 5 mg, chlordiazepoxide 25 mg, lorazepam 1 mg, and oxazepam 15 mg. ^[21]

• Patient is unstable or complications are present: follow ABCDE approach.
  • Start management of complicated AWS as soon as it is suspected.
  • Consider critical care consult.
• Confirm the diagnosis clinically, applying the DSM-5 criteria for AWS.
• Order routine diagnostic studies: e.g., CBC, BMP, serum magnesium, LFTs, INR, albumin, BAC
• Consider investigations for alternate diagnoses: e.g., septic workup, delirium workup, neuroimaging, toxicological screening.
• Identify comorbidities based on clinical suspicion, e.g., alcoholic hepatitis, decompensated liver cirrhosis, pancreatitis.
• Screen for depression and suicidal ideation: e.g., PHQ-2, modified SAD PERSONS scale
• Perform a risk assessment for AWS.
  • Determine disease severity using the CIWA-Ar.
  • Identify risk factors for disease progression: e.g., red flags for AWS, PAWSS score.
• Start pharmacotherapy for AWS (e.g., benzodiazepines) based on the suggested management algorithm for AWS or local protocols.
• Ensure supportive care, e.g., IV fluids, thiamine, treatment of hypoglycemia, and electrolyte repletion.
• Determine disposition and monitoring based on individual risk and severity.
  • Mild AWS (CIWA-Ar < 10) and absent high-risk features: Consider outpatient management; at least daily monitoring for 5 days.
  • All other patients: Usually require inpatient admission; frequent monitoring based on individual risk (e.g., clinical monitoring and CIWA-Ar every 1–4 hours for the first 24 hours)
  • Complicated AWS, poorly controlled or very severe AWS (CIWA-Ar > 35), high benzodiazepine requirement, and/or respiratory complications: Consider ICU admission.

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