Alcohol Withdrawal

Also see: Alcohol Toxicity

The alcohol ingestions most commonly seen in the ED include ethanol, methanol, ethylene glycol, and isopropyl alcohol. Alcohols are primarily metabolized in the liver via alcohol dehydrogenase (ADH) using NAD as a cofactor. In the case of methanol and ethylene glycol it is a metabolite (not the parent compound) that causes severe toxicity, making ADH blockade a key factor in the treatment of these ingestions.

Moderate and severe alcohol withdrawal
- Rapid overview

To obtain emergent consultation with a medical toxicologist, call the United States Poison Control Network at 1-800-222-1222, or access the World Health Organization's list of international poison centers (www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html).
Syndromes
Alcohol tremulousness - occurs early, characterized by hypertension, tachycardia, tremors, and anxiety, with normal mental status
  • 6-8 hours after last drink, lasting 1-3 days
  • Hypersympathetic state: diaphoresis, tremors, anxiety, headache, nausea & vomiting, tachycardia
  • Benzodiazepines; consider clonidine, chlordiazepoxide
    • Chlordiazepoxide 50-100 mg PO q6h x 1 day, then taper: 75 mg q6h day 2, 50 mg q6h day 3, 25 mg q6h day 4
    • Clonidine 0.1-0.2 mg PO TID
Alcohol withdrawal seizures - occurs early, usually single or brief flurry of seizures with short post-ictal period
  • 6-48 hours after last drink; may occur days later
  • Generalized tonic-clonic seizures
  • Treat with benzodiazepines
Alcoholic hallucinosis - occurs early, no evidence of autonomic instability
  • 12-72 hours after last drink; resolves within 24-48 hours
  • Usually visual hallucinations; not related to DTs
  • Treat with benzodiazepines; consider neuroleptic
Delirium tremens - occurs late, characterized by delirium and autonomic instability
  • 48 hours to 2 weeks after last drink lasting 1-5 days; usually preceded by withdrawal seizures
  • Autonomic instability (hyperthermia, severe hypertension, tachycardia, tachypnea), agitation, confusion, visual hallucinations
  • Treat with benzodiazepines; consider addition of propofol, dexmedetomidine, phenobarbital in benzo-resistant patients
Treatment
Benzodiazepines
First line therapy for ALL alcohol withdrawal syndromes
Most patients with symptoms require IV therapy initially
Give:
  • Diazepam, 5 to 10 mg IV, repeat every 5 to 10 minutes
    OR
  • Lorazepam, 1 to 10 mg IV, repeat every 15 to 20 minutes
Massive doses (>2000 mg diazepam in 48 hours) may be required
Clinically stable patients with minimal symptoms may be treated with oral medications
Adjuncts:
  • Haloperidol 5-10 mg IV, IM, PO
  • Propofol 25-200 mcg/kg/min
  • Dexmedetomidine
    • Loading Dose: 1mcg/kg IV over 10 min
    • then 0.2-0.7 mcg/kg/hr
  • Banana Bag: Thiamine 100mg + Mg 2g + multivitamin 1-2 amps.
Delitium Tremers/Withdrawal:
Ativan 0.5 mg
     2t po TID x2d
     2t po BID x2d
     1t po BID x2d
     1t po QD x2d
                 # 26

OR

Librium 25mg
    Day 1 - 4t (100 mg) PO q6h x4 doses
    Day 2 - 3t (75 mg) PO q6h x4 doses
    Day 3 - 2t (50 mg) PO q6h x4 doses
    Day 3 - 1t (25 mg) PO q4h x6 doses
    Day 4 - 1t (25 mg) PO q6h x4 doses
                     # 30
OR

Clonidine 0.1-0.2 mg PO TID

Barbiturates
Synergistic with benzodiazepines; give if patient refractory to high-dose benzodiazepines
Phenobarbital 130 to 260 mg IV, repeat every 15 to 20 minutes
Intubation frequently required with concurrent benzodiazepine and barbiturate use
ALL patients requiring barbiturates are monitored in an intensive care unit
Propofol
Excellent agent if patient refractory to benzodiazepines and barbiturates
Intubation almost always required

1 mg/kg IV push as induction agent for intubation; titrate continuous infusion for sedation

Supportive care
Assure adequate fluid and electrolyte replacement
Give parenteral thiamine 100 mg and glucose daily
Give multivitamin supplements
Ensure adequate caloric support
 

Background

  • Alcohol withdrawal is a life-threatening condition
  • Withdrawal seen after long periods of sustained high blood-alcohol levels
  • Periods and levels causing withdrawal can vary greatly between pts
  • Alcohol  CNS depression; abrupt decrease of alcohol  unmasking of compensatory overactivity in CNS  withdrawal symptoms
  • Important neurotransmitters involved in withdrawal
    • GABA (gamma-aminobutyric acid)
      • Inhibitory neurotransmitter
      • Transmission increased with alcohol ingestion
      • With chronic alcohol use, receptor is downregulated  more alcohol needed to achieve same effects
    • Glutamate
      • Excitatory neurotransmitter acting on NMDA receptor
      • Inhibited by alcohol ingestion
      • Chronic use increases sensitivity  reduction in alcohol level leads to increased excitation
    • Norepinephrine
      • Elevated levels found in CSF of pts undergoing withdrawal
    • Serotonin
      • Involved in tolerance and craving for alcohol
  • Continuum of S/S, severity (incl possible lethality)
Stage I: Minor Withdrawal

Pathophysiology

  • Hypersympathetic state (norepinephrine storm): like hyperthyroidism
    • Withdrawal of anticonvulsant properties of EtOH
    • Hyperactivity of CNS

Symptoms

  • Intention tremor, N/V, tachycardia, HA, hypertension, anxiety, agitation
  • Onset 6-8 hr after last drink; duration 1-3 d
  • Symptoms can begin even with elevated alcohol levels

Labs

  • Electrolytes, BUN/Cr, glucose, Mg, Phos
  • Coags (decr platelet count/function w/ EtOH)
  • Liver enzymes/LFTs
  • UA, HCG in women, urine drug screen if concern for another substance
Treatment
  1. Benzodiazepines
    • Mainstay of treatment of withdrawal symptoms
    • Prevent progression of minor withdrawal symptoms to major; avoid "kindling"
      • Kindling
        • The intensification of withdrawal symptoms with each subsequent withdrawal
        • Repeat withdrawal may lead to increased relapse, brain damage and likelihood of future life threatening withdrawal
           
    • Long acting agents preferred
    • Route of admin depends on clinical setting
    • Fixed dosing or symptom based dosing?
      • Fixed dosing is more commonly used
      • Evidence of symptom based therapy benefit
        • Pts need less medication and have a shorter treatment time
        • Should only be considered for pts without major withdrawal symptoms
           
    • Chlordiazepoxide 75-100 mg PO only
    • Diazepam 2-10 mg IV/PO repeat as needed for objective withdrawal symptoms
    • Lorazepam 1-2 mg IV/PO/IM
      • Less dependent on hepatic metabolism, longer anticonvulsant effects than diazepam
    • Dosing is highly variable for benzodiazepines
  2. Barbiturates
    • Used for pts refractory to benzodiazepines
    • Phenobarbital, propofol
  3. Adjuvant therapy
    • IVF – NS
    • Thiamine (100mg), Mg (2g), MVI (1-2 amps) are commonly added to IV fluid
    • Correct electrolyte abnormalities
  4. Antipsychotics
    • Should only be considered in pts with major withdrawal symptoms (especially hallucinations) not responding to benzos
    • Haloperidol has most favorable side effect profile
Disposition
  1. If reliable, discharge home w/ 3-6 days of medication in a tapering dose
  2. Possible discharge medication protocols
    • Chlordiazepoxide (avoid w/hepatic dz): 100 mg QID day 1, 75 mg QID day 2, 50 mg QID day 3, 25 mg QID day 4
    • Lorazepam: 1 mg QID day 1, TID day 2, BID day 3, qD day 4
    • Phenobarbital: 30 mg QD tapered over 6 days to 5 mg
  3. Other indications for admission
    • Age >60 yo/first episode of ethanol withdrawal, fever, dehydration
    • Resting tachycardia, DBP >100 mmHg, CHF, trauma w/ LOC
    • Cardiac disease, hemodynamic instability, severe acid-base abnormality
    • Severe electrolyte abnormalities, renal insufficiency
    • Resp insufficiency, serious infection, GI bleeding
    • Hyperthermia, rhabdomyolysis
    • History of prior alcohol withdrawal with DT, need for high dose of sedatives to control symptoms

Stage II: Major Withdrawal

Symptoms

  • Marked anxiety
  • Hallucinations
  • Seizures
  • Severe GI symptoms
  • Diaphoresis
  • Confusion – but able to reorient
  • More severe tachycardia (>120 bpm), hypertension

Hallucinations

  • Visual much more common than auditory
    • Auditory more benign
    • Seen in up to 25% chronic alcoholics
  • Autonomic hyperactivity
  • Onset 12-72 hrs, duration 1-2 d
    • Usually 24 hr after lasts drink
  • Less common alcohol-related hallucinosis occurs with clear sensorium, anytime, is auditory, frightening & may be permanent
  • Not related to DTs
    • Clear sensorium even during hallucinations
    • Not the same as DTs
Treatment
  1. Same as previous
  2. Thiamine is essential for any pt with major withdrawal symptoms
    • Prevent/treat Wernicke's encephalopathy
  3. May consider adding haloperidol for hallucinations or severe agitation
Disposition
  1. Admit, monitor closely

Stage III: Seizures

Pathophysiology

  • Most often seen in pts w/ long history of heavy alcohol use
  • 3% of alcoholics have seizures
    • Alcohol is a contributing factor in 20-40% of pts presenting to the ED with seizures
  • EtOH is powerful anticonvulsant (would be an excellent antiseizure medication except for its "side effects")
    • Acute cessation of EtOH is like stopping anticonvulsants

Symptoms

  • Usually abrupt onset, generalized, tonic-clonic, no aura, short post-ictal, rarely tongue biting or incontinence, self limited (very brief)
    • 40% single, 90% 4 or less seizures in 6 hr period
    • 4-8% status epilepticus: get CT scan & metabolite screen
    • 3-20% focal: get CT scan
  • Onset 7-48hr after last drink (95% first 12hr); duration 6-12 hr
  • Can occur as early as 2 hr after last drink

Diagnostic testing

  • Labs
    • Fingerstick glucose
    • Electrolytes, BUN/Cr, glucose, Mg, Phos
    • Coags (decr platelet count and function w/ EtOH)
    • Liver enzymes/LFTs
  • Radiologic
    • Consider CT in all pts (3-6% incidence of unsuspected intracranial pathology: SDH)
  • Any pt with seizure should be evaluated for treatable causes
    • Metabolic – hypoglycemia, hypo/hypernatremia
    • Trauma
    • Infection
    • CVA
    • Non-compliance with seizure meds
    • Drug use other than alcohol
  • Any pt in status epilepticus warrants further workup
    • Mass lesions
    • Infection
Treatment
  1. ABCs, IV, O2, monitor
  2. Benzodiazepines as above
  3. Status epilepticus
    • Aggressive benzodiazepines
      • Diazepam 5-10 mg IV q5min until agitation controlled
        • Rapid onset but shorter duration of action
      • Lorazepam 2-4 mg q10 min
        • Up to 20 mg/hr or 50 mg in hrs
        • Advantages
          • Less sedation in elderly or pts w/liver dz
          • Slower to action but longer duration
          • Longer seizure control because of slow redistribution
    • IVF, thiamine, glucose, (B12 if possible INH)
    • MgSO4 2 g over 20min
    • Phenobarbital (be ready to intubate) 100 mg q1min
    • Carbamazepine contraindicated
Disposition
  1. Admit to ICU

Stage IV: Delirium Tremens

Pathophysiology

  • Overexcitation of central nervous system after alcohol abstinence
  • Serious medical emergency
  • Morbidity/mortality
    • Mortality <6% with aggressive therapy
  • Risk factors for developing DTs
    • History of sustained drinking
    • History of previous DTs
    • Age >30 yo
    • Concurrent illness

Symptoms

  • Global confusion, tremor, agitation, delusions, diaphoresis
  • Hallucinations, anxiety, GI distress, vomiting, delirium
    • Onset 2-5d after last drink (up to 14d); duration 1-5d
    • Usually preceded by withdrawal seizures
  • Low-grade fever, dehydration

Physical Exam

  • Autonomic lability
    • Severe hypertension
    • Severe tachycardia and tachypnea
    • Hyperthermia can be >101

Diagnostic testing

  • Labs
    • Fingerstick glucose
    • Electrolytes (Mg2+), BUN/Cr, glucose
      • Typically higher admission BUN level/low albumin level
    • Toxicologic screen: rule out other co-ingestions if indicated
    • LFTs
    • Coags
  • Consider head CT

Treatment

  1. ABCs, IV, O2, monitor
  2. Benzodiazepines
    • Diazepam, 5 to 10 mg IV, repeat every 5 to 10 minutes (Max: 200 mg)
    • Midazolam, lorazepam
    • Pts in refractory DTs may require extremely large doses of benzos
      • Can also use phenobarbital or propofol
  3. IVF (most pts are hypovolemic)
    • NS
    • K, Mg (10 g 1st day, 5 g each day after)
    • Thiamine, MVI, folate at 250-500 mL/hr
Disposition
  1. DTs must be treated in ICU setting
  2. "Impending DT's" may be treated on floor
    • Seizures to ICU

 

 

Admit Orders: Alcohol Withdrawal

1. Admit to: ICU

2. Diagnosis: Alcohol withdrawals/delirium tremens.

3. Condition: Guarded

4. Vital Signs: q4-6h. Call physician if BP >160/90, <90/60; P >130, <50; R>25, <10; T >38.5°C; or increase in agitation.

5. Activity:

6. Nursing:

7. Diet: Regular, push fluids.

8. IV Fluids: Heparin lock or D5 ½ NS at 100-125 cc/h.

9. Special Medications:

Withdrawal syndrome:

-Lorazepam (Ativan) 1 mg PO tid-qid.


Delirium tremens:

-Diazepam (Valium) 5 mg slow IV push, repeat q6h until calm, then 5-10 mg PO q4-6h OR

-Lorazepam (Ativan) 2 to 4 mg IV, repeated every 15 to 20 minutes.


Seizures:

-Thiamine 100 mg IV push AND

-Dextrose water 50%, 50 mL IV push.

-Lorazepam (Ativan) 0.1 mg/kg IV at 2 mg/min; may repeat x 1 if seizures continue.

Wernicke-Korsakoff Syndrome:

-Thiamine 100 mg IV stat, then 100 mg IV qd.

 

Mild Symptom Treatment (score less than or equal to 8):

  • No treatment, reassess in 4 hours


Moderate Symptoms (score 9-15):

  • Chlordiazepoxide (Librium) 50 mg by mouth every 2 hours (if able to take po medications)
    Reassess score in 2 hours and administer medication according to score.
    Maximum Daily dose is 300mg within 24 hours.
    Lorazepam (Ativan) 2 mg IV every 4 hours (if unable to take po medications)
    Reassess score in 2 hours and administer medication according to score.
    Maximum Daily dose is 24 mg within 24 hours.
    Hold for excessive sleeping, hypotension (MAP less than 65 or SBP less than 90 or DBP less than 60)
     

Severe Symptoms (Score greater than 15):

  • Chlordiazepoxide (Librium) 50 mg by mouth every 1 hour (if able to take po medications)
    Reassess score in 1 hour and administer medication according to score.
    Maximum Daily dose is 300mg within 24 hours
    Lorazepam (Ativan) 2 mg IV every 1 hour (if unable to take po medications)
    Reassess score in an hour and administer medication according to score.
    Maximum Daily dose is 24 mg within 24 hours.
    Hold for excessive sleeping, hypotension (MAP less than 65 or SBP less than 90 or DBP less than 60)


10. Symptomatic Medications:

-Multivitamin 1 amp IV, then 1 tab PO qd.

-Folate 1 mg PO qd.

-Thiamine 100 mg PO qd.

-Acetaminophen (Tylenol) 1-2 PO q4-6h prn headache.

- Banana Bag daily (Thiamine 100mg, Folic acid 1mg, Magnesium Sulfate 2 Grams and 1 MVI ( 10ml ) in 1000 ml over 4 hours (Mix with D5W or D5NS)

- Nicotine patch 21mg / day

- Ondansetron (Zofran) 4 milligrams IV every 4 hrs. prn nausea

- DVT Proph.


11. Extras:
 CXR, ECG. Alcohol rehabilitation consult.

12. Labs: CBC, CMP, Mg, amylase, liver panel, urine drug screen. UA, INR/PTT.