· Hallucinations that develop within 12 to 24 hours of abstinence and typically resolve within 24 to 48 hours
· Hallucinations are usually visual, although auditory and tactile phenomena are also described.
2) Delirium Tremens:
· Typically begins between 48 and 96 hours after the last drink and lasts one to five days
Risk Factors for DT :
A history of alcohol withdrawal seizures
A history of sustained drinking
A history of Delirium Tremens (Altered mental status)
Age greater than 30
presence of a concurrent illness
The presence of significant alcohol withdrawal in the presence of an elevated blood alcohol concentration
A longer period since the last drink
General Factors to Consider:
Quantity of alcoholic intake
Duration of alcohol use
Time since last drink
Previous alcohol withdrawals
Presence of concurrent medical or psychiatric conditions
Abuse of other agents.
Should assess possible complicating medical conditions: Arrhythmias, CHF, CAD, gastrointestinal bleeding, infections, liver disease, nervous system impairment, and pancreatitis.
Complete blood count
Liver function tests
Urine drug screen
Determination of blood alcohol and electrolyte levels.
CIWA SCORE - Clinical Institute Withdrawal Assessment for Alcohol
Criteria: N/V, Anxiety, Paroxysmal sweats, Tactile disturbances, Visual disturbances, tremors, agitation, orientation and cloudiness of the sensorium, Auditory disturbances, Headache
Scale for Scoring: Total Score
0 – 9: absent or minimal withdrawal
10 – 19: mild to moderate withdrawal
More than 20: severe withdrawal
1) Ruling out alternative diagnoses
It may be necessary to perform extensive testing, including lumbar puncture and cranial computed tomography (CT), to rule out other diagnostic considerations with confidence
Especially, Important when the presentation includes altered mental status and fever.
Factors such as infections, trauma metabolic derangements, drug overdose, hepatic failure, and gastrointestinal bleeding can mimic or coexist with alcohol withdrawal
A premature diagnosis of alcohol withdrawal can lead to inappropriate use of sedatives, which can further delay accurate diagnosis
2) Supportive Care
Benzodiazepines are used to control psychomotor agitation and prevent progression to more severe withdrawal
Supportive care, including intravenous IV fluids, nutritional supplementation, and frequent clinical reassessment including vital signs
Patients should be placed in a quiet, protective environment.
Isotonic IV fluid can be infused rapidly until patients are clinically euvolemic
Thiamine (100 milligrams IV) followed by glucose should be administered in order to prevent or treat Wernicke encephalopathy.
Multivitamins containing or supplemented with folic acid (Vit B9) should be given routinely, and deficiencies of glucose, potassium, magnesium, and phosphate should be corrected as needed
Neurologic complication of thiamine (vitamin B1) deficiency
Thiamine (B1) protects agents oxidative stress
Thiamine has a role in cerebral energy utilization – Deficiency leads to neuronal injury by inhibiting metabolism in brain regions with high metabolic requirements
Alcohol leads to reduced absorption as it causes inflammation to the GIT
Common Symptoms include: Ataxia, confusion, ocular muscle disturbances
Neuronal damage occurs usually after 14 days of deficiency (about 20% below normal)
200-500mg thiamine IV TID until symptom resolution.
Replete glucose and magnesium shortly after.
Usually irreversible condition due to chronic thiamine deficiency resulting in in neuronal death
Common symptoms: Amnesia, poor recall, confabulation.
Memory disorder despite appearance of no cognitive losses.
Recent memory most effected.
50% will have permanent impairment after repletion
Even after thiamine repletion 75% of patients will have some long-term changes – permanent impairment (amnesia).
· Used to treat the psychomotor agitation most patients experience during withdrawal and to prevent progression from minor withdrawal symptoms to major ones
· Diazepam (Valium), lorazepam (Ativan), and chlordiazepoxide (Librium) are used most frequently to treat or prevent alcohol withdrawal, but other benzodiazepines may be used .
· In general, long-acting benzodiazepines with active metabolites (ex, diazepam or chlordiazepoxide) are preferred because they seem to result in a smoother clinical course with lower chance of recurrent withdrawal or seizures
u Lorazepam oral dosing: 2 mg orally every 6 hours for 4 doses, then 1 mg every 6 hours for 8 doses
u Lorazepam IV dosing: 2 to 4 mg IV every 15 to 20 minutes
u Diazepam IV dosing: 5 to 10 mg IV every 5 to 10 minutes
· lorazepam (Ativan) or oxazepam (Serax) are preferred for the treatment of patients with advanced cirrhosis or acute alcoholic hepatitis.
· The shorter half-life of lorazepam and the absence of active metabolites with oxazepam may prevent prolonged effects if over sedation occurs.
· Chlordiazepoxide has a relatively long half-life and may lead to over sedation in patients with severe liver disease
BZD Mechanism of Action
· Positive Allosteric modulators. They bind between Alpha and Gamma subunits
· When BZD are bound, Cl- channel opens longer, which enhances the amount of Cl- entering the cell
· They only work in the presence of GABA. So with prolonged heavy Alcohol use -
u Cross tolerance between BZDs and Alcohol.
1) Loading Dose Strategy
· Uses high doses of longer‐acting benzodiazepines to quickly achieve initial sedation with a self‐tapering effect over time due to their pharmacokinetic properties.
· Typically, diazepam 10–20 mg or chlordiazepoxide 100 mg doses are repeated every 1–2 h until the patient reaches adequate sedation with an average of three doses usually required
· Possible Benefits: Reducing the total of BZDs needed, and intense monitoring is usually required in the earlier part
· Possible Drawbacks: Sedation and respiratory depression- need to intensely monitor (especially in elderly patients or those with hepatic dysfunction).
2) Fixed or Scheduled dosing
· Beneficial for patients who will require medication regardless of symptoms, such as in those with a history of seizures or DT
· Also used in patients withdrawing from alcohol with comorbid medical illnesses or if unable to assess withdrawal symptoms.
· Chlordiazepoxide and diazepam remain the agents of choice because of their long‐acting nature
· A ceiling dose of 60 mg of diazepam or 125 mg of chlordiazepoxide is advised per day
After 2–3 d of stabilization of the withdrawal syndrome, the benzodiazepine is gradually tapered off over a period of 7–10 days
3) Symptom Triggered therapy
· Requires regular assessment of patient's withdrawal symptoms using a validated tool like the CIWA scale
· Not applicable in non‐verbal patients
· The cutoff for beginning treatment is a score of at least 8
· 5–10 mg diazepam or 25–100 mg chlordiazepoxide
· If symptoms persist, doses are repeated hourly until the score is below 8.
· Advantages: Lower doses of BZDs used, less sedation, and lower risk of respiratory depression
· 1. At low doses: They act like BZD (positive allosteric modulators) as they Increase Cl- entry when they bind between the Alpha and Beta subunits.
· 2. At high doses, they can open GABA-A Cl- channels on their own even when GABA is not present.
· 3. Barbiturates can inhibit Glutamate (excitatory) neurotransmitters. Antagonists at the AMPA receptors.
· In patients with refractory Delirium tremens or Alcohol withdrawal seizures who require high doses of BZD
· Pts with Chronic heavy Alcohol use who have cross tolerance between Alcohol and BZD
· Phenobarbital Dosing: 130 to 260 mg IV, repeated every 15 to 20 minutes, until symptoms are controlled
Monitoring/ considerations & Precautions
u Do not start benzodiazepines after starting phenobarbital
u Phenobarbital loading doses may need to be reduced in patients with higher risk of sedation or respiratory compromise
u Patients receiving phenobarbital must be on a cardiac monitor with continuous oxygen saturation monitoring