Alcohol withdrawal

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Key Recommendations

The main goals of treatment are to reduce symptoms of withdrawal, help with long-term abstinence, and detect and treat concurrent medical or psychiatric illness.[83] Early identification of the signs and symptoms of withdrawal, and prompt treatment, can lower the risk of progression to severe or complicated alcohol withdrawal syndrome (AWS).[5] Treatment includes management of acute withdrawal symptoms and prevention of relapse. Relapse can be managed by counseling strategies or pharmacotherapy.

If the patient’s clinical condition permits, treatment for alcohol use disorder (AUD) should be commenced simultaneously with that for alcohol withdrawal.[5]

See topic Alcohol use disorder.

Supportive care is critical and should include patient education about the process of alcohol withdrawal and common symptoms, regular reassurance and reorientation, good nursing care, as well as frequent psychologic review and reassessment of suicide risk.[5]

Management decisions should be based on the severity of AWS, using a validated assessment scale such as Clinical Institute Withdrawal Assessment for Alcohol scale, revised version (CIWA-Ar).[5] CIWA-Ar Opens in new window

Outpatient management

Patients with minor AWS, with a CIWA-Ar score of <10, can be treated as outpatients, although this is not routinely recommended without adequate assessment and support, due to the likely clinical risks and low likelihood of success.[12] If patients are managed in the community, they require clear follow-up precautions, prompt referral to specialist alcohol nurse, and regular scheduled contact with a health professional for physical and psychosocial reassessment.[5][6][12]

Treatment may only need to be supportive, or pharmacotherapy can be used.[5][6] Patients with moderate to severe AWS (CIWA-Ar >10) require pharmacotherapy.[5][6] Patients with an unstable home environment or severe AWS require hospital management consisting of pharmacologic and supportive interventions.

People who are alcohol dependent but not admitted to the hospital should be advised to avoid a sudden reduction in alcohol intake and should be provided with information about how to contact local alcohol support services or referred to an appropriate treatment program.[8]

If a patient presents to the emergency department, they can be discharged for management in the ambulatory setting if:[5]

their symptoms of withdrawal are mild (CIWS-Ar <10) or moderate (with no complicating factors)
the patient is not currently intoxicated
there is no history of complicated alcohol withdrawal or alcohol withdrawal seizures
no significant medical or psychiatric comorbidities
they appear able to attend outpatient visits and follow-up appointments.

Short-term prescriptions for medication to control/prevent alcohol withdrawal can be provided by the emergency department, provided appropriate, timely follow-up is scheduled.[5]

Hospital admission criteria

The following patients should be admitted to hospital for medically assisted alcohol withdrawal:[8]

Those with moderate to severe AWS, or those who are assessed to be at high risk of developing alcohol withdrawal seizures or alcohol withdrawal delirium (also known as delirium tremens).
Young people (under 16 years of age) with moderate to severe AWS (who will also require physical and psychosocial assessment in hospital).
Certain vulnerable people with moderate to severe AWS (e.g., those who are frail, have cognitive impairment or multiple comorbidities, lack social support, have learning difficulties, or are aged 16 or 17 years).

In addition, patients with decompensated medical disease, major electrolyte abnormalities, CIWA-Ar score >15 when serum ethanol is <20 mg/dL, or a history of alcohol withdrawal delirium or alcohol withdrawal seizures should be considered for admission.[84]

Hospital admission should also be considered for patients presenting to primary care, or who had been managed as an outpatient, with:[5][6]

Agitation or severe tremor, unresolved with adequate medical treatment, and requires continuous monitoring
Development of signs or symptoms of severe withdrawal (e.g., persistent vomiting, marked agitation, hallucinations, confusion, seizure, CIWA-Ar >19)
Deterioration of an existing medical or psychiatric condition
Oversedation on outpatient medical management
Resumption of alcohol use
Any evidence of clinical instability (e.g., syncope, unstable vital signs)
Patients who are pregnant.

All patients in hospital need close monitoring for delirium, in line with local guidelines, electrolyte repletion and intravenous fluid infusion as indicated, as well as regular vital signs, fluid intake and output, and serum electrolytes.[5]

Patients with severe AWS and associated psychiatric or medical conditions require high levels of care (e.g., possible intensive care unit [ICU] admission - see ICU admission criteria below) and increased benzodiazepine doses. Morbidity and mortality is greater among this patient population. A subset of patients with severe AWS are benzodiazepine resistant and may require adjunctive agents for treatment.[85][86] Clinically, patients requiring ≥50 mg of intravenous diazepam in the first hour of treatment are considered to have benzodiazepine-resistant AWS.[87]

Other patient groups who require intensive monitoring include:

Those who have an alcohol withdrawal seizure; reassess every 1-2 hours for 6-24 hours.[5] These patients should be monitored as inpatients for at least 36-48 hours after the seizure, to ensure there are no further seizures and alcohol withdrawal delirium does not develop.[88]
Patients who are agitated or delirious; should have continuous, one-to-one observation.[5]
Patients requiring pharmacotherapy, or with moderate to severe AWS; monitor closely and reassess every 1-4 hours, as clinically indicated.[5]

Gradual reduction in monitoring frequency can occur once the patient becomes medically stable. In patients with mild symptoms and low risk of severe or complicated AWS, monitoring can cease after 36 hours, as more severe withdrawal is very unlikely to subsequently develop.

For more information on monitoring, see Monitoring.

ICU admission criteria

Admission to the ICU is indicated in patients with hemodynamic instability, severe electrolyte abnormalities, cardiac disease, respiratory distress, potential severe infections, persistent hyperthermia, signs of gastrointestinal pathology, evidence of rhabdomyolysis, renal insufficiency, need for frequent or high doses of sedatives (including benzodiazepines and barbiturates), or endotracheal intubation, or with symptoms of withdrawal despite elevated serum ethanol concentration.[89] In practice, patients might be admitted to a critical care setting without meeting these criteria if they would benefit from enhanced monitoring and nursing support. Patients with alcohol withdrawal delirium require close nursing observation and supportive care, which often necessitates admission to an intensive or critical care unit.[5]

Benzodiazepines

Benzodiazepines are first-line agents for the pharmacologic management of alcohol withdrawal symptoms and seizures related to alcohol withdrawal.[5][7][15][18][89][90][91] [ ] [Evidence B] The European Academy of Neurology (EAN) guidelines on alcohol-related seizures, and other sources, recommend lorazepam and diazepam as drugs of choice.[7][89]

In patients with alcohol withdrawal seizures, benzodiazepines are more effective than placebo.[92] [ ] [Evidence B] No single benzodiazepine is superior to another, although some (nonsignificant) data suggest that chlordiazepoxide may be more effective than other agents.[92][93] Oral medication is appropriate for mild withdrawal, but intravenous administration of benzodiazepines is preferred for moderate to severe AWS. Intramuscular administration of lorazepam may be appropriate before obtaining intravenous access. In patients with hepatic failure, lorazepam may be preferred over chlordiazepoxide to avoid the risk of increased sedation.[5]

Alcohol withdrawal seizures are usually self-limited; recurrent seizures or status epilepticus should be managed with benzodiazepines, but they should also prompt investigation for other causes of the seizures. For the initial treatment of alcohol-related status epilepticus, intravenous lorazepam is considered safe and efficacious.[7] Intravenous diazepam is a good alternative.[7][89]

Antipsychotic medications, such as haloperidol, are not recommended as they have not been shown to confer benefit and have the potential to lower the seizure threshold.

Benzodiazepine doses used in AWS treatment regimens may be much higher than recommended doses for other indications. Complications of benzodiazepine therapy include oversedation and, less commonly, respiratory depression. Frequent assessment is therefore required. Long-acting benzodiazepines are preferred, but in patients with liver disease, short-acting benzodiazepines are used to prevent oversedation.[6] Clinicians should be aware of the risks of additive effects of longer-acting agents; multiple doses administered within a short time period can lead to oversedation and respiratory depression, especially in patients who have taken other respiratory depressants such as opioids.[5] Airway obstruction can occur in those who lose pharyngeal muscle tone, especially in the setting of elevated body mass index (BMI) or a history of obstructive sleep apnea.[94]

There are three approaches to treatment of AWS with benzodiazepines:[5][95]

Symptom-triggered: treating with medication when the CIWA-Ar scores are above 8 points. This is the preferred dosing method.[5]
Fixed-dose regimen: doses are administered at specific time intervals and additional doses may be given as required based on symptoms. If prescribing a shorter-acting benzodiazepine, a fixed-dose regimen with a gradual taper may be appropriate to reduce the likelihood of breakthrough and rebound signs and symptoms.[5]
Front-loading regimen for patients at high risk of severe withdrawal: a high dose of long-acting medication is given to achieve rapid symptom control.[5] Recommended medication for the front-loading regimen is diazepam or chlordiazepoxide.[5] This treatment approach has been shown to reduce the incidence of alcohol withdrawal seizures and delirium in high-risk patients.[5]

A front-loading regimen may be recommended for patients at high risk of severe withdrawal.[5] A single dose can be administered to patients with a history of severe AWS, a concomitant acute medical or surgical complaint, severe coronary artery disease, or in patients showing clinical evidence of AWS with a positive blood ethanol level.[5] Patients with significant cardiovascular comorbidities require aggressive withdrawal treatment due to the potentially harmful effects of autonomic hyperactivity.[5]

Outpatient regimens are usually fixed-dose regimens to reduce the risk of breakthrough or rebound symptoms.[5] For outpatients in whom initial treatment fails, higher doses of benzodiazepines or alternative medications may be required, and the patient may need to be admitted to the hospital for further management.[5] Patients admitted will need continuous cardiac and pulse oximetry monitoring, and, potentially, ICU-level care.

To minimize the risk of benzodiazepine dependence or misuse, patients who are managed in the outpatient setting should be prescribed only the minimum amount of medication; the prescription should be discontinued as soon as treatment is complete.[5]

Patients taking benzodiazepines should be educated about side effects such as drowsiness and drug interactions with other central nervous system depressants and when combined with alcohol. Patients should also be advised not to drive or operate heavy machinery while taking benzodiazepines.[5]

Other pharmacotherapies

Patients with severe AWS and/or alcohol withdrawal delirium resistant to increased doses of benzodiazepines, or where there is high risk of severe or complicated AWS may benefit from phenobarbital as an alternative to benzodiazepines.[5][85][96][97] It is also appropriate for initial therapy in patients with a contraindication for benzodiazepines, when managed by a clinician experienced with its use.[5] In some studies, phenobarbital has been associated with a reduction in need for mechanical ventilation and reduced ICU admissions and ICU/hospital length of stay, although other data do not show significant difference in clinical course/outcome.[96][97][98][99] Parenteral phenobarbital should only be used in ICU, or in areas with high levels of monitoring.[5]

Dexmedetomidine, a sedative agent (alpha-2 adrenergic agonist), may be used alonside benzodiazepines for the management of AWS in the ICU setting if autonomic hyperactivity, anxiety, and agitation/delirium are not adequately controlled with benzodiazepines alone.[5][100] Evidence for the use of dexmedetomidine in AWS is limited. Data from one small randomized trial suggest that patients receiving dexmedetomidine may require reduced doses of benzodiazepine.[101] Similar findings have been reported in case series.[102] Dexmedetomidine lacks gamma-aminobutyric acid (GABA) receptor activity and does not reduce withdrawal-related seizures. One study has demonstrated excess adverse mortality in critically ill patients under 65 years receiving dexmedetomidine as sedation in ICU.[103] Therefore, dexmedetomidine should only be prescribed as an adjunct to a benzodiazepine and its use considered carefully.

Propofol, an anesthetic agent, is reserved for patients resistant to benzodiazepine therapy or those requiring mechanical ventilation.[104] It appears to be effective but is associated with significant increases in clinical care, including length of ICU and length of hospital stay.[18][105] Propofol can cause respiratory depression; patients started on propofol must be admitted to the ICU and are usually intubated.

Vitamin supplementation

Vitamin supplementation should be considered in patients with AUD and likely vitamin deficiencies. Thiamine supplementation reduces the risk of Wernicke encephalopathy and Korsakoff syndrome.[5] Chronic alcohol consumption results in reduced absorption of thiamine; therefore, intravenous or intramuscular administration is recommended.[18] Patients should be managed in a monitored setting due to the risk of potentially serious allergic adverse reactions that may occur during or shortly after parenteral administration. High-dose thiamine is given if Wernicke encephalopathy is suspected.[15] All patients with AWS admitted to the ICU should receive thiamine.[5] In the outpatient setting, oral thiamine can be offered.[5]

Folate replacement should be considered in critically ill patients because AUD is associated with hyperhomocysteinemia.[5]

Electrolyte and fluid replacement

Correct any electrolyte abnormalities, including glucose, calcium, potassium, phosphorus, and magnesium. Dehydration due to vomiting, diarrhea, or other insensible losses may need correction with intravenous fluids.

There is no evidence to support the use of magnesium for treatment or prophylaxis of AWS.[5] However, magnesium should be used to correct hypomagnesemia in those with AUD and is indicated in patients with cardiac arrhythmias, electrolyte abnormalities (e.g., hypokalemia), or a history of alcohol withdrawal seizures.[5] Severe hypomagnesemia (<1 mg/dL) and symptomatic patients in the emergency setting may need up to 2 g/day of magnesium sulfate given by intravenous infusion. The patient should be managed in a monitored setting. Deep tendon reflexes and respiratory rate and pattern should be periodically assessed to monitor for hypermagnesemia. Further management of hypomagnesemia should be performed in consultation with a hospital specialist and also with a primary care physician.

Replacement of phosphorus is recommended in the presence of deficiency. If deficiency is mild, replacement can be oral/dietary, with intravenous supplementation if levels are lower than 1 mg/dL.

Further management

Following successful management of withdrawal symptoms, patients should be referred to cognitive behavioral therapy, a support group, or medical management to prevent continued alcohol abuse.

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