Background

Physiologic basics

• Alcohol is believed to potentiate the actions of GABA, a major inhibitory neurotransmitter, and suppress the actions of glutamate, a major excitatory neurotransmitter.
• Rapid cessation of alcohol use results in overall CNS hyperactivity and lower seizure threshold.
  • Opposite of depressant effects of alcohol (increased adrenergic, serotonergic, and cholinergic activity).

Risk factors

• Prior withdrawal is a risk factor for future episodes.
• Prior alcohol withdrawal seizures is a risk factor for more severe alcohol withdrawal.
• 50% of persons with history of long term, heavy alcohol use will have mild alcohol withdrawal.
  • 10% of symptomatic individuals will progress.
    • Generalized tonic clonic seizures.
      • If left untreated, 1/3 of patients with withdrawal seizures will progress to delirium tremens.
    • Delirium tremens occurs in 3-5% of patients hospitalized for management of alcohol withdrawal.

Clinical Presentation

Signs and symptoms

• Tremulousness: 6-12 hours after last drink. Occurs in 75-100%. Resolves in 24-48 hours.
• Irritability, diaphoresis, GI upset, tachycardia, HTN, tremor of hands, tongue wag.
• Seizures: 12-48 hours after last drink; an early phenomenon. Very rarely status epilepticus.
• If the patient is febrile, seizure is focal, or if the patient has no history of seizures, evaluate for secondary seizure (LP, CT, electrolytes, tox screen, etc.).
• Alcoholic hallucinations: 25% of patients within 12-24 hours after the last drink and can persist for days. Patient’s sensorium is clear except for auditory and/or visual hallucinations.
• Delirium tremens: 2-7 days after last drink. 4-5% of patients.
  • This is a MEDICAL EMERGENCY with 5% mortality (often due to PNA or arrhythmia).
  • Usually lasts several days. Marked by clouded consciousness, delirium, diaphoresis, agitation, hallucinations (visual> tactile> auditory), and autonomic instability (hypertension, tachycardia, low grade fever [<38.5˚C]).
  • For DT symptoms lasting >7 days or worsening despite high doses of benzodiazepines, consider other causes of delirium including benzodiazepine induced, or GHB/baclofen withdrawal syndromes which can present like DTs but can be benzodiazepine resistant.

DSM5 definition of alcohol withdrawal (all 4 must be present):

• Cessation or reduction of alcohol use that has been heavy and prolonged.
• Two or more of following developing within hours to days of cessation or reduction in alcohol use:
  • Autonomic hyperactivity.
  • Increased hand tremor.
  • Insomnia.
  • Nausea or vomiting.
  • Transient visual, tactile or auditory hallucinations.
  • Anxiety.
  • GTC seizures.
• Signs and symptoms cause clinically significant distress or impairment in social, occupational or other important areas of functioning.
• Signs or symptoms are not attributable to another medical condition, mental disorder, or another substance intoxication or withdrawal.

Severe alcohol withdrawal syndrome: intense autonomic and psychological symptoms AND withdrawal seizures, delirium tremens, or both.

 

Initial Assessment

• Airway, breathing, circulation, disability.
• Recognition of concurrent trauma.
• Administer thiamine for empiric prevention of Wernicke’s encephalopathy (WE) or Korsakoff’s psychosis.
  • If WE clinically suspected, administer thiamine 500 mg IV q8h for 72h.
  • If low suspicion for WE, administer thiamine 100 mg daily. Thiamine should be replete IV x 3 days in the acute setting due to minimal PO absorption.
• Evaluate for hypovolemia as there is high prevalence of intravascular volume depletion among people who use alcohol.
  • If volume depleted, administer IV fluid bolus.
• Evaluate for electrolyte disturbances (Mg and K are often severely depleted). Many patients require several days of supplementation.
• Start all patients on folate 1 mg daily and multivitamin supplementation.
• If patient is actively seizing, administer benzodiazepines:
  • Diazepam 5-10 mg IV, repeated in 5-10 minutes if needed.
  • Lorazepam 2-4 mg IV, repeated in 5-10 minutes if needed.
  • Midazolam 2-4 mg IM, if no IV access.
• If patient is in status epilepticus:
  • Secure airway.
  • Admit to ICU.
  • Progression from benzodiazepines to phenytoin/fosphenytoin, to phenobarbital, to valproic acid, to propofol and pentobarbital.
• Further evaluation:
  • For all alcohol withdrawal hospitalizations, evaluate for co-occurring medical conditions (alcoholic hepatitis, pancreatitis, cirrhosis, gastrointestinal bleed, infection, trauma, hypoglycemia, co-ingestions, arrhythmias, dilated cardiomyopathy, altered electrolytes).
  • If febrile, rule out infection.
  • Ethanol level is generally not helpful; negative level does not rule out withdrawal, and some patients show signs of withdrawal with toxic ethanol levels. Consider sending if history or presentation is unclear.
  • Check ECG if considering giving haloperidol as part of treatment.

Management

PAWSS (Prediction of Alcohol Withdrawal Severity Scale)

• Consists of 3 parts: 1) threshold criteria 2) patient questions 3) clinical evaluation.

• Once risk for withdrawal assessed, determine need for initiation of alcohol withdrawal treatment.
• Use a CIWA protocol (see below) to administer benzodiazepines with or without adjunctive haloperidol.
• Can also start adjunctive gabapentin (300-600 TID) to decrease benzodiazepine requirements. Limited data for gabapentin in alcohol use disorder treatment.
• Seizure precautions if deemed at risk.
• Assessment for alcohol use disorder and motivational interviewing.

CIWA

• CIWA was originally designed as a tool for alcohol withdrawal research and is validated only in mild to moderate alcohol withdrawal.
  • Studies on CIWA have frequently excluded patients with seizures.
  • CIWA does not include vital sign assessment, which is an important part of recognizing severe alcohol withdrawal syndrome.       
• Systematic reviews show no difference between different benzodiazepines (BZD).
  • Consider lorazepam for use in the elderly, those with liver disease, or if NPO.
  • Do not mix BZD (e.g., if using lorazepam scheduled, use lorazepam for breakthrough).
  • Oral administration is preferred, as is symptom-triggered rather than a standing administration.
    • Symptom triggered protocols are preferred over fixed dose protocols given decreased mean amount of BZD used, decreased total duration of treatment and decreased length of hospital stay.

Assess CIWA score: < 8 = not yet in withdrawal, > 8 = withdrawing, > 25 = needs monitoring.

• CIWA scores can be calculated online or with set protocol forms.

Withdrawal prophylaxis

• Use only if initial CIWA < 8 (not in withdrawal). Assess CIWA and sedation scale every 6 hours and 1 hour after admin of BZD. Hold BZD for sedation, assess vitals.
• Assess risk class based on history, degree of alcohol abuse, etc. Risk level:
  • Mild: diazepam 5 mg PO/IV, or chlordiazepoxide 25 mg PO, or lorazepam 1 mg PO/IV/SL/IM every 6 hours and q1h prn for CIWA > 8.
  • Moderate: diazepam 10 mg PO/IV, or chlordiazepoxide 50 mg PO, or lorazepam 2 mg as above.
  • Severe: diazepam 20 mg PO/IV, chlordiazepoxide 75-100 mg PO, or lorazepam 3-4 mg as above.

Initial treatment of acute withdrawal

• CIWA 8-25. Goal is to achieve CIWA < 8.
• Assess CIWA and sedation scale every 4 hours and 1 hour after admin of BZD. Hold BZD for sedation, assess vitals.
  • Mild (CIWA 8-15): diazepam 10 mg PO/IV, or chlordiazepoxide 50 mg PO, or lorazepam 1-2 mg PO/IV/SL/IM q 1 hour x 2.
  • Moderate (CIWA 16-25): diazepam 20 mg PO/IV, or chlordiazepoxide 100 mg PO, or lorazepam 3-4 mg PO/IV/SL/IV q 1 hour x 2.

 Ongoing treatment of acute withdrawal

• CIWA < 8 after treatment of acute withdrawal. Goal is to keep CIWA < 8.
• Diazepam 10-20 mg PO/IV, or chlordiazepoxide 50-100 mg PO (NTE 600 mg/24 hours), or lorazepam 3-4 mg PO/IV/SL/IM every 6 hours ATC and q1h prn CIWA > 8.
• Taper benzodiazepines by 25% per day once stable for 24 hours.
   

Treatment of severe withdrawal

• CIWA > 25 or uncontrolled severe symptoms.
• Transfer/admit to monitored setting with continuous oxygen and telemetry.
• CIWA and sedation score every 2 hours and 15-30 min after IV BZD administration.
• Diazepam 10-20 mg IV or lorazepam 2-4 mg IV every 15-30 minutes for six hours.
  • Titrate to CIWA < 8 or moderate sedation.
  • If total requirements are > 200 mg diazepam in 3 hours (or > 40 mg lorazepam), consider starting gtt or benzo refractory adjuncts. Be aware that the carrier agents in some IV lorazepam preparations can themselves be toxic (propylene glycol).
• Taper by 25% per day once stable CIWA < 8. Allow PRN boluses for breakthrough.
• Adjuncts: consider in consultation with Critical Care/Poison Control if benzodiazepine- refractory:
  • Phenobarbital for withdrawal seizures, initial dose of 260 mg IV, then 130 mg every 30 minutes until signs of mild intoxication.
  • Dexmedetomidine (DEX) may be considered as an adjunct to benzodiazepines in treating symptoms of autonomic hyperactivity.
    • Does not have anti-convulsant prosperities.
    • Insufficient data to determine if DEX will reduce need for intubation or affect length of stay.
  • Propofol may be considered as an adjunct to benzodiazepines but does not appear to offer advantage over benzodiazepines or DEX.
    • Studies report higher incidence of cardiovascular effects, mechanical ventilation, pneumonia.
    • Use only in patients who have failed or cannot tolerate other agents.

Example protocols:

• Use of barbiturate only (phenobarbital) or barbiturate/benzodiazepine combination protocols have been shown to be effective.

• Consider use of adjuvant pharmacologic therapy:
  • Gabapentin 1800 mg/day used during first 2 days of hospital admission significantly lowered total dose of benzodiazepines.
    • Gabapentin appears to be more beneficial for mild rather than severe alcohol withdrawal.
    • High dose Gabapentin (1800 mg/day) is also associated with decrease in percentage of heavy drinking days.

 

CIWA protocol adapted from San Francisco General Hospital CIWA protocol form.

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