Alcohol withdrawal

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

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

all patients

1st line – benzodiazepine or phenobarbital

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1st line –

benzodiazepine or phenobarbital

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][92] [ ] [Evidence B] The European Federation of Neurological Societies 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 (only available as an oral formulation in the US) 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 alcohol withdrawal syndrome (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 should also prompt investigation for other causes of seizures. For the initial treatment of alcohol-related status epilepticus, intravenous lorazepam is considered safe and efficacious.[7][89] Intravenous diazepam is a good alternative.[7][89]

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. 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 or a history of obstructive sleep apnea.[94]

There are three approaches to treatment of AWS with benzodiazepines:[5][95] (1) symptom-triggered: treating with medication when the patient's Clinical Institute Withdrawal Assessment for Alcohol scale, revised version (CIWA-Ar) score is above 8 points; this is the preferred dosing method; (2) fixed-dose regimen: where doses are administered at specific time intervals and additional doses may be given as required based on symptoms; (3) 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.[5] If prescribing a shorter-acting benzodiazepine, a fixed-dose regimen with a gradual taper may be appropriate to reduce the risk of breakthrough or rebound symptoms.[5] For outpatients in whom 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]

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 immediately 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 or when combined with alcohol. Patients should also be advised not to drive or operate heavy machinery while taking benzodiazepines.[5]

A subset of patients with severe AWS is described as benzodiazepine resistant and may require adjunctive agents for AWS 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]

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]

Primary options

chlordiazepoxide: consult local protocols for guidance on dose

diazepam: consult local protocols for guidance on dose

lorazepam: consult local protocols for guidance on dose

Secondary options

phenobarbital: consult local protocols for guidance on dose

Plus – supportive care

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Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

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] Treatment should also include prevention of relapse. Relapse can be managed by counseling strategies or pharmacotherapy.

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

Patients with mild alcohol withdrawal syndrome (AWS), with a Clinical Institute Withdrawal Assessment for Alcohol scale, revised version (CIWA-Ar) score of <10, can be treated as outpatients with follow-up precautions. Patients with an unstable home environment or severe AWS require in-hospital management consisting of pharmacologic and supportive interventions.

Admission to hospital for medically assisted alcohol withdrawal should be offered to the following people:[8] those with moderate to severe AWS who are assessed to be at high risk of developing alcohol withdrawal seizures or alcohol withdrawal delirium; young people under 16 years of age with moderate to severe AWS; 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 16 or 17 years of age).

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]

Patients with severe AWS and associated psychiatric or medical conditions require high levels of care (e.g., intensive care unit [ICU] admission) and increased benzodiazepine doses. Morbidity and mortality is greater among this patient population.

Patients who have an alcohol withdrawal seizure also require intensive monitoring; 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 should be monitored closely and reassessed every one to four 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.

See Monitoring.

ICU admission 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]

Patients admitted to hospital will need continuous cardiac and pulse oximetry monitoring and, potentially, ICU care.

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

Consider – vitamin supplementation

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Consider –

vitamin supplementation

Treatment recommended for SOME patients in selected patient group

Vitamin supplementation should be considered in patients with alcohol use disorder (AUD) and likely vitamin deficiencies.

Thiamine supplementation reduces the risk of Wernicke encephalopathy and Korsakoff syndrome.[5] Chronic alcohol consumption results in reduced gastrointestinal absorption of thiamine; therefore, intravenous or intramuscular administration is recommended.[18] Patients should be managed in a monitored setting because of 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 alcohol withdrawal syndrome (AWS) admitted to the intensive care unit 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]

Primary options

thiamine (vitamin B1): prevention of Wernicke encephalopathy: 100-200 mg intravenously/intramuscularly/orally once daily for 3-5 days; treatment of Wernicke encephalopathy: 200-500 mg intravenously/intramuscularly three times daily for 2-7 days, followed by 250 mg intravenously/intramuscularly once daily for 3-5 days, then 100 mg orally once daily

and

folic acid (vitamin B9): 0.4 to 1 mg intravenously/orally once daily

Consider – electrolyte and fluid replacement

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Consider –

electrolyte and fluid replacement

Treatment recommended for SOME patients in selected patient group

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 specific dose of magnesium used to correct hypomagnesemia in chronic alcoholism and in patients with cardiac arrhythmias, electrolyte abnormalities 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 done in consultation with a hospital specialist and also with a primary care physician.

Replacement of phosphorus is recommended in the presence of deficiency.[5] If deficiency is mild, replacement can be oral/dietary, with intravenous supplementation if levels are lower than 1 mg/dL.[5]

Consult local protocols to determine doses for electrolyte replacement.

with severe alcohol withdrawal syndrome, intensive care unit admission

Consider – dexmedetomidine

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Consider –

dexmedetomidine

Treatment recommended for SOME patients in selected patient group

Dexmedetomidine, a sedative agent (alpha-2 adrenergic agonist), may be used alonside benzodiazepines for the management of alcohol withdrawal syndrome (AWS) in the intensive care unit (ICU) setting, if autonomic hyperactivity and anxiety are not adequately controlled with benzodiazepines alone.[5]

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.

Primary options

dexmedetomidine injection: consult local protocols for guidance on dose

with benzodiazepine-resistant severe alcohol withdrawal syndrome, intensive care unit admission

Consider – propofol

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Alcohol withdrawal

all patients

benzodiazepine or phenobarbital

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

supportive care

vitamin supplementation

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

electrolyte and fluid replacement

with severe alcohol withdrawal syndrome, intensive care unit admission

dexmedetomidine

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

with benzodiazepine-resistant severe alcohol withdrawal syndrome, intensive care unit admission

propofol

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Alcohol withdrawal

Treatment algorithm

all patients

benzodiazepine or phenobarbital

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

supportive care

vitamin supplementation

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

electrolyte and fluid replacement

with severe alcohol withdrawal syndrome, intensive care unit admission

dexmedetomidine

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

with benzodiazepine-resistant severe alcohol withdrawal syndrome, intensive care unit admission

propofol

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options