Alcohol Withdrawal

See Also

Epidemiology

Onset: 6-24 hours after last Alcohol intake
Duration: 5-7 days after abstinence
Peak symptoms: 1-3 days after abstinence

Pathophysiology

Occurs after daily heavy Alcohol use for at least 2 weeks
Abrupt Alcohol cessation results in unmasked compensatory mechanisms for chronic Alcohol Abuse
1. Disinhibition of alpha-2 receptors
2. Increases Catecholamine levels at presynaptic membranes

Risk Factors
Complicated Withdrawal

History of Delirium Tremens or Alcohol Withdrawal Seizures
Multiple Prior Withdrawal Episodes
Comorbid Illness
Age >65 years old
Long duration of heavy Alcohol consumption
Seizures during current withdrawal episode
Significant autonomic hyperactivity on presentation (Tachycardia, Hypertension)
Physiologic dependence on GABAergic agents (Benzodiazepines, Barbiturates)

Risk Factors
Severe Withdrawal (Delirium Tremens)

Age >30-40 years
Heavy drinking >8 years
Alcohol intake >100 grams, >1 pint liquor, >96 oz beer
Patient experiences withdrawal symptoms when abstinent
Hepatic Cirrhosis
Lab abnormalities
1. Mean Corpuscular Volume (MCV) increased
2. Blood Urea Nitrogen (BUN) increased
3. Blood Alcohol Level >0.20 g/dl on random draw
Reference
1. Ferguson (1996) J Gen Intern Med 11:410-4 [PubMed]

Symptoms

Stage 1 - Initial Withdrawal Symptoms (6-12 hours after last Alcohol)
1. Anxiety or Panic Attacks
2. Anorexia
3. Paresthesias
4. Shakes, Jitters or Tremors
5. Chills, Sweats, or Fevers
6. Chest Pain or Palpitations
7. Insomnia
8. Headache
9. Nausea or Vomiting
10. Abdominal Pain
11. Still coherent
Alcohol Hallucinations or Alcoholic hallucinosis (12-24 hours after last Alcohol)
1. Affects 8% of Alcohol Withdrawal patients
2. Paranoid Delusions or Illusions
3. Tactile Hallucinations (common)
4. Auditory and Visual Hallucinations (less common)
5. Sensorium otherwise maintained
Stage 2 - Withdrawal Seizures and autonomic hyperactivity (24-72 hours post-Alcohol)
1. Marked Agitation, restlessness and diaphoresis
2. Tremulous with constant eye movements
3. Nausea, Vomiting, Anorexia, and Diarrhea
4. Sinus Tachycardia >120 bpm
5. Systolic Hypertension with SBP >160 mmHg
6. Confusion may be present
7. Withdrawal Seizures (24-48 hours post-Alcohol)
  1. Generalized tonic-clonic Seizures
  2. Brief Seizures (<5 minutes) and may recur
  3. Isolated and self limited (Status Epilepticus is not due to withdrawal)
Stage 3 - Delirium Tremens (72-96 hours)
1. Of those with withdrawal Seizures, 33% progress to DTs
2. Fluctuating disturance of attention, awareness, orientation, memory, language and visuospatial ability
3. Visual Hallucinations
4. Disorientation and Delirium
5. Autonomic instability
  1. Severe Tachycardia and Hypertension
  2. Severe Agitation and tremulousness
  3. Hyperthermia (Fever, severe diaphoresis)
Resolution
1. Resolves at 5-7 days

Signs

Blood Pressure, pulse and Temperature elevated
Hyperarousal, Agitation, or Restlessness
Cutaneous Flushing or Diaphoresis
Dilated pupils
Ataxia
Altered Level of Consciousness or Disorientation
Delirium Tremens

Labs

Complete Blood Count
Comprehensive metabolic panel
1. Serum Electrolytes
2. Renal Function tests
3. Liver Function Tests
Serum Magnesium
ProTime (INR)
1. Increased INR is a marker of advanced liver dysfunction
Drug screen
1. Blood Alcohol Level
2. Urine Drug Screen
Other testing to consider in risk for multiple ingestion or toxic Alcohol ingestion
1. Salicylate Level
2. Acetaminophen Level
3. Serum Osmolality
  1. Consider in suspected toxic Alcohol ingestion (Methanol, Polyethylene glycol)
4. Venous Blood Gas (VBG)

Diagnostics

Electrocardiogram (EKG)
1. Evaluate for QT Prolongation, QRS Widening (as in Unknown Ingestion)
2. Evaluate for Acute Coronary Syndrome
Consider other testing if suspicious of underlying infection

Diagnosis
DSM-5 Criteria Alcohol Withdrawal

Heavy Alcohol usage for a prolonged period (>2 weeks) followed by Alcohol cessation or reduction
Signs or symptoms cause significant distress or Impairment of functioning and not explained by other condition
Two or more of the following, developing several hours to a few days after Alcohol cessation or reduction
1. Autonomic hyperactivity (e.g. diaphoresis, Tachycardia >100 bpm)
2. Increased hand Tremor
3. Insomnia
4. Nausea or Vomiting
5. Transient auditory, visual or Tactile Hallucinations or Illusions
6. Psychomotor Agitation
7. Anxiety
8. Generalized Tonic Clonic Seizures
Modifiers
1. With perceptual disturbance
  1. Visual or Tactile Hallucinations occur with intact reality testing OR
  2. Auditory, visual or Tactile Hallucinations when Delirium is absent

Grading

See Clinical Institute Withdrawal Assessment for Alcohol (CIWA)
See Short Alcohol Withdrawal Scale (SAWS)
Mild Alcohol Withdrawal
1. Mild to moderate anxiety
2. Sweating
3. Insomnia
Moderate Alcohol Withdrawal
1. Moderate Anxiety
2. Mild Tremor
Severe Alcohol Withdrawal
1. Severe Anxiety
2. Moderate to severe Tremor
Complicated Alcohol Withdrawal
1. Alcohol Withdrawal Seizures
2. Confusion
3. Delirium

Differential Diagnosis

See Altered Level of Consciousness
See Sympathomimetic Toxicity
See Unknown Ingestion or Overdose
Wernicke's Encephalopathy
Agitated Delirium
Acute Psychosis
Serotonin Syndrome
Thyrotoxicosis
Infection or Sepsis
Electrolyte abnormalities (e.g. Hyponatremia, Hypokalemia)
Thyrotoxicosis
Acute blood loss (e.g. Trauma, Gastrointestinal Bleeding)
Closed Head Injury
Intracranial Hemorrhage (e.g. Subdural Hematoma, Subarachnoid Hemorrhage)
Meningitis or Encephalitis

Complications
Delirium Tremens

Head Trauma
Myocardial Infarction
Aspiration Pneumonia and other infections
Electrolyte disturbance (e.g. Hypomagnesemia)
Death
1. Delirium Tremens has a 5-10% mortality rate

Management
General Measures

Seizure precautions
Supplementation
1. Vitamin Deficiency is common (Vitamins A, C, B1, B3, B6, B9, B12)
  1. See Alcohol Dependence
2. Thiamine (Vitamin B1) 100 mg orally daily
3. Folate (Vitamin B9) 1 mg orally daily
4. Multivitamin daily
5. Treat Hypomagnesemia if present
Intravenous Fluids (Normal Saline or banana bag)
1. Frequently administered to intoxicated patients admitted to the Emergency Department
2. IV Fluids do not shorten the length of ED stay for intoxicated patients (typical ED stay averages 4.5 hours)
  1. Perez (2013) Emerg Med Australas 25(6): 527-34 [PubMed]

Management
Disposition

See Clinical Sobriety
Facility Level Indications
1. Level 1 Withdrawal Management: Outpatient Clinic
  1. Mild Alcohol Withdrawal (CIWA <=10)
2. Level 2 Withdrawal Management: Onsite Monitoring (e.g. Detox and CD treatment Centers)
  1. Mild or Moderate Alcohol Withdrawal (CIWA <=18)
  2. Complicated withdrawal risk factors (see above)
  3. Opioid Use Disorder (or physiologic Opioid Dependence)
  4. Severe Alcohol Withdrawal within the last year
  5. Seizure Disorder
3. Inpatient Withdrawal Management
  1. Severe Alcohol Withdrawal (CIWA >18)
  2. Complicated withdrawal symptoms
  3. Active psychiatric conditions
  4. Unstable chronic condition
  5. Inability to tolerate oral intake
  6. Clinical significant abnormal lab testing
    1. Serious Electrolyte abnormalities
    2. Significant Acute Kidney Injury

Management
Agents used in Alcohol Withdrawal

Also see Alcohol Detoxification in Ambulatory Setting
Benzodiazepines
1. See dosing potocols below
2. Early aggressive Benzodiazepine loading offers best Alcohol Withdrawal control
3. Benzodiazepines are the primary agent in moderate to severe Alcohol Withdrawal
  1. Reduces Alcohol Withdrawal Seizure risk
  2. Reduces Delirium Tremens risk
4. Precautions
  1. Monitor for over-sedation and respiratory depression (esp. concomitant liver disease)
5. Agent Selection
  1. Agents with long half-life are preferred for most patients (lower rebound risk)
    1. Valium
    2. Librium
      1. Librium has less stimulation of reward system (lower abuse potential)
  2. Seizure history
    1. Valium
  3. Liver disease or elderly patient (use agents with less hepatic metabolism)
    1. Ativan
    2. Serax
Benzodiazepine Alternatives (in patients in whom Benzodiazepines are considered too risky, commonly used in Europe)
1. Precautions
  1. Carbamazepine, Gabapentin and Valproic Acid have not been shown to prevent Alcohol Withdrawal Seizure
  2. Carbamazepine, Gabapentin and Valproic Acid increase GABA (via Sodium channel blockade)
  3. Adverse risks include Thrombocytopenia and other Bone Marrow suppression, Pancreatitis
2. Carbamazepine
  1. Effective in mild to moderate withdrawal
  2. Protocol 1: Tapered
    1. Tapered 200 mg four times daily tapered over 5 days
    2. Start at Carbamazepine (Tegretol) 800 mg on day 1
    3. Finish at 200 mg once on day 5
  3. Protocol 2: Constant
    1. Carbamazepine 200 mg every 8 hours or 400 mg every 12 hours
  4. References
    1. Malcolm (2002) J Gen Intern Med 17:349-55 [PubMed]
3. Gabapentin
  1. Potentiates CNS GABA activity and decreases glutamate activity
    1. Decreases Alcohol craving and depression
  2. Dosing (minimum effective daily dose 900 mg/day)
    1. Start 600 mg three times daily for 3 days
    2. Then 300 mg three times daily for 3 days
  3. References
    1. Stock (2013) Ann Pharmacother 47: 961-9 [PubMed]
    2. Myrick (2009) Alcohol Clin Exp Res 33(9): 1582-8 +PMID:19485969 [PubMed]
4. Valproic Acid
  1. Has also been used in Alcohol Withdrawal
  2. Not recommended for monotherapy (may be used as adjunct with Benzodiazepines)
  3. Avoid in severe liver disease or pregnancy
  4. Dosing 300 mg to 500 mg every 6 hours
Adjunctive agents that may require airway and ventilation management (see severe Alcohol Withdrawal protocol below)
1. Phenobarbital
  1. See Phenobarbital Single Agent Protocol below
  2. Avoid IV infusion >60 mg/min
  3. Phenobarbital 5-10 mg/kg IBW up to 130 to 260 mg every 20-30 minutes titrating to light sedation
  4. Nisavic (2019) Psychosomatics 60(5):458-67 [PubMed]
  5. Nelson (2019) Am J Emerg Med 37(4):733-6 [PubMed]
  6. Tidwell (2018) Am J Crit Care 27(6):454-60 [PubMed]
2. Propofol infusion
3. Dexmedetomidine (Precedex)
Other symptomatic agents
1. Beta Blockers (e.g. Metoprolol)
  1. Avoid in general as these mask withdrawal signs
  2. Symptomatic relief of chills, shakes
  3. Improves Vital Signs
  4. Use selective Beta Blocker in Coronary Artery Disease
    1. Metoprolol Tartrate (Lopressor) 25 to 50 mg orally every 12 hours
2. Haloperidol
  1. Decreases Agitation and Hallucinations
  2. May lower Seizure threshold (but typically does not cause recurrent Seizures)

Management
Mild Alcohol Withdrawal Protocol (CIWA-Ar 10 or less, SAWS <12)

See Outpatient Alcohol Withdrawal Protocol
Indications
1. Mild Alcohol Withdrawal (CIWA-Ar <=10, SAWS <12)
2. No Complicated Withdrawal Risk Factors (see above)
3. If criteria not met, proceed to Mild Alcohol Withdrawal protocol as below
Contraindications
1. Lack of reliable social support
2. Lack of safe home environment
3. Able to sustain daily reevaluation
Disposition
1. Outpatient Clinic
Education
1. Review Alcohol Withdrawal expected course
2. Review signs of severe Alcohol Withdrawal
3. Maintain home low-stimulation environment
4. Maintain hydration with non-caffeinated fluid
Other measures
1. Thiamine 100 mg daily for 5 days
2. Multivitamin orally daily
3. Gabapentin (Neurontin) may be considered (may reduce craving)
  1. Start 600 mg three times daily for 3 days
  2. Then 300 mg three times daily for 3 days
  3. Does NOT prevent withdrawal Seizures or Delirium Tremens
Monitoring
1. Evaluations may be performed by any health care professional (e.g. RN, medical provider)
2. Daily reevaluation for up to 5 days
  1. Modify based on symptom severity (increased or decreased)
3. Face to face evaluations with Vital Signs are preferred
  1. Telemedicine may be used as needed
  2. Evaluate withdrawal severity
    1. Record Blood Pressure, Heart Rate
    2. Obtain Alcohol breath analysis
    3. Calculate CIWA-Ar or SAWS
  3. Symptom and sign review
    1. Hydration
    2. Sleep
    3. Mental status
    4. Mood
    5. Suicidality
    6. Substance use
4. Indications for Emergent referral to higher level of care (detox center, emergency department)
  1. Continued symptoms refractory to multiple doses of withdrawal medications
  2. Worsening or severe symptoms
  3. Persistent Vomiting
  4. Hallucinations
  5. Confusion
  6. Seizures

Management
Mild to Moderate Alcohol Withdrawal Protocol (CIWA-Ar 10 to 15, or Complicated withdrawal risk factors)

Indications
1. Mild or Moderate Alcohol Withdrawal (CIWA 10 to 15) OR
2. Complicated withdrawal risk factors (see above)
Disposition
1. Level 2 Withdrawal Management: Onsite Monitoring (e.g. Detox and CD treatment Centers)
2. Level 1 Outpatient Clinic if no complicated withdrawal risk factors
  1. See Outpatient Alcohol Withdrawal Protocol
General Symptom Triggered Protocol (based on CIWA-Ar or SAWS)
1. Diazepam (Valium) 5-10 mg orally every 6-8 hours prn for 1-3 days OR
2. Lorazepam (Ativan) 1-2 mg orally every 4-6 hours prn for 1-3 days OR
3. Chlordiazepoxide (Librium) 25-50 mg orally every 6-8 hours for 1-3 days
Defining Criteria and Additional Medication Indications
1. Systolic Blood Pressure > 150 mmHg
2. Diastolic Blood Pressure > 90 mmHg
3. Heart Rate > 100
4. Temperature > 37.7 C (100 F)
5. Tremulousness, Insomnia, or Agitation

Management
Moderate to Severe Alcohol Withdrawal Protocol (CIWA-Ar 16-20)

Indications: Defining Criteria and Additional Medication Indications
1. Systolic Blood Pressure: 150-200 mmHg
2. Diastolic Blood Pressure: 100-140 mmHg
3. Heart Rate: 110-140
4. Temperature: 37.7 to 38.3 C (100 to 101 F)
5. Tremulousness, Insomnia, or Agitation
Disposition
1. Level 2 Withdrawal Management: Onsite Monitoring (e.g. Detox and CD treatment Centers) OR
2. Inpatient medical facility
Symptom-Triggered Regimen (preferred)
1. Preferred in moderate to severe Alcohol Withdrawal
2. Based on Clinical Institute Withdrawal Assessment (CIWA-Ar)
  1. http://addiction-medicine.org/files/15doc.html
  2. Assess hourly to determine medication need
3. Give one of following hourly until CIWA-Ar <8-10 points
  1. Chlordiazepoxide (Librium) 50 to 100 mg
  2. Diazepam (Valium) 10 to 20 mg
  3. Lorazepam (Ativan) 2 to 4 mg
  4. Oxazepam (Serax) 15 to 30 mg
Fixed-Dose Protocol
1. Diazepam (Valium)
  1. Day 1: 15 to 20 mg orally four times daily
  2. Day 2: 10 to 20 mg orally four times daily
  3. Day 3: 5 to 15 mg orally four times daily
  4. Day 4: 10 mg orally four times daily
  5. Day 5: 5 mg orally four times daily
2. Lorazepam (Ativan)
  1. Days 1-2: 2-4 mg orally four times daily
  2. Days 3-4: 1-2 mg orally four times daily
  3. Day 5: 1 mg orally twice daily
3. Chlordiazepoxide (Librium)
  1. Day 1: 50-100 mg orally four times daily
  2. Days 2-4: 25-50 mg orally four times daily
  3. Decrease by 20% per day

Management
Severe Alcohol Withdrawal Protocol (CIWA-Ar >20, with maximum score 67)

Indicated in Delirium Tremens
Disposition
1. Inpatient Facility Intensive Care Unit
General Protocol (Requires ICU observation)
1. Endpoint: until adequate sedation (RASS Score 0 to -2) and improved CIWA-Ar score
2. Diazepam (Valium)
  1. Start: 10-20 mg IV every 5-15 min prn
  2. Titrate dose for refractory symptoms to 20 mg, then 40 mg, then 80 mg
3. Lorazepam (Ativan)
  1. Start: 2-4 mg IV every 15-20 min prn
  2. Titrate dose for refractory symptoms to 4 mg, then 8 mg, then 16 mg, then 32 mg
4. Chlordiazepoxide (Librium)
  1. Start: 25 to 100 mg IM/IV every 1-4 hours (max: 300 mg/day)
Defining Criteria and Additional Medication Indications
1. Systolic Blood Pressure > 200 mmHg
2. Diastolic Blood Pressure > 140 mmHg
3. Heart Rate > 140
4. Temperature > 38.3 C (101 F)
5. Tremulousness, Insomnia, or Agitation
Adjunctive measures (may require Advanced Airway and Ventilatory support)
1. Phenobarbital 10 mg/kg up to 130-260 mg IV prn
2. Propofol induction (RSI), followed by intubation and Propofol infusion
3. Dexmedetomidine (Precedex) 0.2 to 0.6 mcg/kg/hour up to 1.2 mg/kg/hour
  1. Do not reduce Benzodiazepine dose when used with Dexmedetomidine
4. Ketamine (NMDA antagonist)
  1. May reduce Benzodiazepine requirement in severe Alcohol withdawal (ICU patients)
  2. Ketamine 0.2 g/kg/hour infusion (avoid doses 0.3 to 1 g/kg/hour)
  3. Wong (2015) Ann Pharmacother 49(1):14-9 +PMID:25325907 [PubMed]
  4. Pizon (2018) Crit Care Med 46(8):e768-71 +PMID:29742583 [PubMed]
  5. Shah (2018) J Med Toxicol 14(3): 229-36 +PMID:29748926 [PubMed]

Management
Phenobarbital Single Agent Protocol

Indications
1. Alcohol Withdrawal AND
2. No Benzodiazepines or other sedating medications given AND
3. No other active neurologic problems
Precautions
1. Do NOT combine with Benzodiazepines or other sedating medications
2. Dosing listed here is for adults only
Protocol
1. IV Phenobarbital Load
  1. Phenobarbital 10 mg/kg Ideal Body Weight (IBW) over 30 minutes
  2. Wait 30 minutes before any additional Phenobarbital given
2. IV Phenobarbital Titration
  1. Up to every 30 minutes give one of the 2 following doses as needed (no maximum, titrate to effect)
  2. Mild Symptoms: 130 mg IV over 3 minutes every 30 minutes as needed
  3. Severe symptoms 260 mg IV over 5 minutes every 30 minutes as needed
3. Oral or IM Phenobarbital Maintenance (non-ED or ICU setting)
  1. Up to every 60 minutes give one of the 2 following doses as needed
  2. Mild Symptoms: 100 mg oral or IM every 60 minutes as needed
  3. Severe symptoms 200 mg oral or IM every 60 minutes as needed

Prevention

See Alcohol Abuse Management
Following Alcohol treatment program and aftercare are critical following Alcohol Withdrawal protocol

Resources
Patient Education

Information from your Family Doctor: Alcohol Withdrawal
1. http://www.familydoctor.org/handouts/007.html

References

Cardy, Swadron, Nordt in Herbert (2018) EM:Rap 18(8): 9-11
Ferri (2001) Care of Medical Patient, p. 802-5
Leaf and Musgrave (2017) Crit Dec Emerg Med 31(7): 15-20
McMicken in Marx (2002) Rosen Emergency Med, p. 2513-16
Orman and Hayes (2015) EM:Rap 15(11): 7-8
Orman and Starr (2015) EM:Rap 15(12): 10-11
Bayard (2004) Am Fam Physician 69(6):1443-50 [PubMed]
Chang (2001) Med Clin North Am 85(5):1191-212 [PubMed]
Muncie (2013) Am Fam Physician 88(9): 589-95 [PubMed]
Tiglao (2021) Am Fam Physician 104(3): 253-62 [PubMed]