II. Epidemiology
III. Pathophysiology
- Occurs after daily heavy Alcohol use for at least 2 weeks
- Abrupt Alcohol cessation results in unmasked compensatory mechanisms for chronic Alcohol Abuse
- Disinhibition of alpha-2 receptors
- Increases Catecholamine levels at presynaptic membranes
- Decreases GABA (Gamma-Aminobutyric Acid) levels
- GABA is an inhibitory Neurotransmitter that decreases Neuron excitability
- Alcohol increases GABA levels, resulting in relaxation and mental slowing
- Heavy chronic Alcohol use down regulates GABA Receptors, resulting in less GABA response
- Alcohol Withdrawal stems in part from a drop in GABA levels and an increase in Glutamate (excitatory Neurotransmitter)
- Many of the drugs used in Alcohol Withdrawal are active in stimulating GABA activity
- Phenobarbital is a direct GABA A receptor Agonist
- Benzodiazepines enhance activity at GABA A receptors, but do not directly bind GABA Receptors
- Timing
- Onset: 6-24 hours after last Alcohol intake
- Duration: 5-7 days after abstinence
- Peak symptoms: 1-3 days after abstinence
IV. 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)
V. 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
- Mean Corpuscular Volume (MCV) increased
- Blood Urea Nitrogen (BUN) increased
- Blood Alcohol Level >0.20 g/dl on random draw
- Reference
VI. Symptoms
- Stage 1 - Initial Withdrawal Symptoms (6-12 hours after last Alcohol)
- Anxiety or Panic Attacks
- Anorexia
- Paresthesias
- Shakes, Jitters or Tremors
- Chills, Sweats, or Fevers
- Chest Pain or Palpitations
- Insomnia
- Headache
- Nausea or Vomiting
- Abdominal Pain
- Still coherent
- Alcohol Hallucinations or Alcoholic hallucinosis (12-24 hours after last Alcohol)
- Affects 8% of Alcohol Withdrawal patients
- Paranoid Delusions or Illusions
- Tactile Hallucinations (common)
- Auditory and Visual Hallucinations (less common)
- Sensorium otherwise maintained
- Stage 2 - Withdrawal Seizures and autonomic hyperactivity (24-72 hours post-Alcohol)
- Marked Agitation, restlessness and diaphoresis
- Tremulous with constant eye movements
- Nausea, Vomiting, Anorexia, and Diarrhea
- Sinus Tachycardia >120 bpm
- Systolic Hypertension with SBP >160 mmHg
- Confusion may be present
- Withdrawal Seizures (24-48 hours post-Alcohol)
- Generalized tonic-clonic Seizures
- Brief Seizures (<5 minutes) and may recur
- Isolated and self limited (Status Epilepticus is not due to withdrawal)
- Stage 3 - Delirium Tremens (72-96 hours)
- Of those with withdrawal Seizures, 33% progress to DTs
- Fluctuating disturance of attention, awareness, orientation, memory, language and visuospatial ability
- Visual Hallucinations
- Disorientation and Delirium
- Autonomic instability
- Severe Tachycardia and Hypertension
- Severe Agitation and tremulousness
- Hyperthermia (Fever, severe diaphoresis)
- Resolution
- Resolves at 5-7 days
VII. 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
VIII. Labs
- Complete Blood Count
- Comprehensive metabolic panel
- Serum Electrolytes
- Renal Function tests
- Liver Function Tests
- Serum Magnesium
-
ProTime (INR)
- Increased INR is a marker of advanced liver dysfunction
- Drug screen
- Other testing to consider in risk for multiple ingestion or Toxic Alcohol ingestion
- Salicylate Level
- Acetaminophen Level
- Serum Osmolality
- Consider in suspected Toxic Alcohol ingestion (Methanol, Polyethylene Glycol)
- Venous Blood Gas (VBG)
IX. Diagnostics
-
Electrocardiogram (EKG)
- Evaluate for QT Prolongation, QRS Widening (as in Unknown Ingestion)
- Evaluate for Acute Coronary Syndrome
- Consider other testing if suspicious of underlying infection
X. 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
- Autonomic hyperactivity (e.g. diaphoresis, Tachycardia >100 bpm)
- Increased hand Tremor
- Insomnia
- Nausea or Vomiting
- Transient auditory, visual or Tactile Hallucinations or Illusions
- Psychomotor Agitation
- Anxiety
- Generalized Tonic Clonic Seizures
- Modifiers
- With perceptual disturbance
- Visual or Tactile Hallucinations occur with intact reality testing OR
- Auditory, visual or Tactile Hallucinations when Delirium is absent
- With perceptual disturbance
XI. Grading
- See Clinical Institute Withdrawal Assessment for Alcohol (CIWA)
- See Short Alcohol Withdrawal Scale (SAWS)
- Mild Alcohol Withdrawal
- Mild to moderate anxiety
- Sweating
- Insomnia
- Moderate Alcohol Withdrawal
- Moderate Anxiety
- Mild Tremor
- Severe Alcohol Withdrawal
- Severe Anxiety
- Moderate to severe Tremor
- Complicated Alcohol Withdrawal
XII. 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
XIII. Complications: Delirium Tremens
- Head Trauma
- Myocardial Infarction
- Aspiration Pneumonia and other infections
- Electrolyte disturbance (e.g. Hypomagnesemia)
- Death
- Delirium Tremens has a 5-10% mortality rate
XIV. Management: General Measures
- Seizure precautions
- Correct Electrolyte abnormalities as needed
- Supplementation
- Vitamin Deficiency is common (Vitamins A, C, B1, B3, B6, B9, B12)
- Thiamine (Vitamin B1) 100 mg orally daily
- If Wernicke's Encephalopathy is suspected, Thiamine 500 mg IV every 8 hours is initiated
- Folate (Vitamin B9) 1 mg orally daily
- Multivitamin daily
-
Intravenous Fluids (Normal Saline or banana bag)
- Frequently administered to intoxicated patients admitted to the Emergency Department
- IV Fluids do not shorten the length of ED stay for intoxicated patients (typical ED stay averages 4.5 hours)
XV. Management: Disposition
- See Clinical Sobriety
- Facility Level Indications
- Level 1 Withdrawal Management: Outpatient Clinic
- Mild Alcohol Withdrawal (CIWA <=8)
- Level 2 Withdrawal Management: Onsite Monitoring (e.g. Detox and CD treatment Centers)
- Mild or Moderate Alcohol Withdrawal (CIWA 8 to 15)
- Complicated withdrawal risk factors (see above)
- Opioid Use Disorder (or physiologic Opioid Dependence)
- Severe Alcohol Withdrawal within the last year
- Seizure Disorder
- Inpatient Withdrawal Management
- Severe Alcohol Withdrawal (CIWA >15 )
- Complicated withdrawal symptoms
- Active psychiatric conditions (e.g. Psychosis)
- Unstable chronic condition
- Inability to tolerate oral intake
- Clinical significant abnormal lab testing
- Serious Electrolyte abnormalities
- Significant Acute Kidney Injury
- Level 1 Withdrawal Management: Outpatient Clinic
XVI. Management: Agents used in Alcohol Withdrawal
- Also see Alcohol Detoxification in Ambulatory Setting
- See below for the Phenobarbital Single Agent Alcohol Withdrawal Protocol
- Phenobarbital as a single agent is also considered first-line in Alcohol Withdrawal
-
Benzodiazepines
- See dosing potocols below
- Early aggressive Benzodiazepine loading offers best Alcohol Withdrawal control
- Benzodiazepines are the primary agent in moderate to severe Alcohol Withdrawal
- Reduces Alcohol Withdrawal Seizure risk
- Reduces Delirium Tremens risk
- Precautions
- Monitor for over-sedation and respiratory depression (esp. concomitant liver disease)
- Agent Selection
-
Benzodiazepine Alternatives (in patients in whom Benzodiazepines are considered too risky, commonly used in Europe)
- Precautions
- Carbamazepine, Gabapentin and Valproic Acid have not been shown to prevent Alcohol Withdrawal Seizure
- Carbamazepine, Gabapentin and Valproic Acid increase GABA (via Sodium channel blockade)
- Adverse risks include Thrombocytopenia and other Bone Marrow suppression, Pancreatitis
- Carbamazepine
- Effective in mild to moderate withdrawal
- Protocol 1: Tapered
- Tapered 200 mg four times daily tapered over 5 days
- Start at Carbamazepine (Tegretol) 800 mg on day 1
- Finish at 200 mg once on day 5
- Protocol 2: Constant
- Carbamazepine 200 mg every 8 hours or 400 mg every 12 hours
- References
- Gabapentin
- Valproic Acid
- Has also been used in Alcohol Withdrawal
- Not recommended for monotherapy (may be used as adjunct with Benzodiazepines)
- Avoid in severe liver disease or pregnancy
- Dosing 300 mg to 500 mg every 6 hours
- Precautions
- Adjunctive agents that may require airway and ventilation management (see severe Alcohol Withdrawal Protocol below)
- Phenobarbital
- See Phenobarbital Single Agent Protocol below (safe without airway compromise risk)
- Avoid IV infusion >60 mg/min
- Phenobarbital 5-10 mg/kg IBW up to 130 to 260 mg every 20-30 minutes titrating to light sedation
- Nisavic (2019) Psychosomatics 60(5):458-67 [PubMed]
- Nelson (2019) Am J Emerg Med 37(4):733-6 [PubMed]
- Tidwell (2018) Am J Crit Care 27(6):454-60 [PubMed]
- Propofol infusion
- Dexmedetomidine (Precedex)
- Phenobarbital
- Other symptomatic agents
- Beta Blockers (e.g. Metoprolol)
- Avoid in general as these mask withdrawal signs
- Symptomatic relief of chills, shakes
- Improves Vital Signs
- Use selective Beta Blocker in Coronary Artery Disease
- Metoprolol Tartrate (Lopressor) 25 to 50 mg orally every 12 hours
- Haloperidol
- Decreases Agitation and Hallucinations
- May lower Seizure threshold (but typically does not cause recurrent Seizures)
- Beta Blockers (e.g. Metoprolol)
XVII. Management: Mild Alcohol Withdrawal Protocol (CIWA-Ar 10 or less, SAWS <12)
- See Outpatient Alcohol Withdrawal Protocol
- Indications
- Contraindications
- Lack of reliable social support
- Lack of safe home environment
- Able to sustain daily reevaluation
- Disposition
- Outpatient Clinic
- Education
- Review Alcohol Withdrawal expected course
- Review signs of severe Alcohol Withdrawal
- Maintain home low-stimulation environment
- Maintain hydration with non-caffeinated fluid
- Other measures
- Thiamine 100 mg daily for 5 days
- Multivitamin orally daily
- Gabapentin (Neurontin) may be considered (may reduce craving)
- Start 600 mg three times daily for 3 days
- Then 300 mg three times daily for 3 days
- Does NOT prevent withdrawal Seizures or Delirium Tremens
- Monitoring
- Evaluations may be performed by any health care professional (e.g. RN, medical provider)
- Daily reevaluation for up to 5 days
- Modify based on symptom severity (increased or decreased)
- Face to face evaluations with Vital Signs are preferred
- Telemedicine may be used as needed
- Evaluate withdrawal severity
- Record Blood Pressure, Heart Rate
- Obtain Alcohol breath analysis
- Calculate CIWA-Ar or SAWS
- Symptom and sign review
- Hydration
- Sleep
- Mental status
- Mood
- Suicidality
- Substance use
- Indications for Emergent referral to higher level of care (detox center, emergency department)
- Continued symptoms refractory to multiple doses of withdrawal medications
- Worsening or severe symptoms
- Persistent Vomiting
- Hallucinations
- Confusion
- Seizures
XVIII. Management: Mild to Moderate Alcohol Withdrawal Protocol (CIWA-Ar 10 to 15, or Complicated withdrawal risk factors)
- Indications
- Mild or Moderate Alcohol Withdrawal (CIWA 10 to 15) OR
- Complicated withdrawal risk factors (see above)
- Disposition
- Level 2 Withdrawal Management: Onsite Monitoring (e.g. Detox and CD treatment Centers)
- Level 1 Outpatient Clinic if no complicated withdrawal risk factors
- General Symptom Triggered Protocol (based on CIWA-Ar or SAWS)
- Defining Criteria and Additional Medication Indications
- Systolic Blood Pressure > 150 mmHg
- Diastolic Blood Pressure > 90 mmHg
- Heart Rate > 100
- Temperature > 37.7 C (100 F)
- Tremulousness, Insomnia, or Agitation
XIX. Management: Moderate to Severe Alcohol Withdrawal Protocol (CIWA-Ar 16-20)
- Indications: Defining Criteria and Additional Medication Indications
- Systolic Blood Pressure: 150-200 mmHg
- Diastolic Blood Pressure: 100-140 mmHg
- Heart Rate: 110-140
- Temperature: 37.7 to 38.3 C (100 to 101 F)
- Tremulousness, Insomnia, or Agitation
- Disposition
- Level 2 Withdrawal Management: Onsite Monitoring (e.g. Detox and CD treatment Centers) OR
- Inpatient medical facility
- Symptom-Triggered Regimen (preferred)
- Preferred in moderate to severe Alcohol Withdrawal
- Based on Clinical Institute Withdrawal Assessment (CIWA-Ar)
- http://addiction-medicine.org/files/15doc.html
- Assess hourly to determine medication need
- Give one of following hourly until CIWA-Ar <8-10 points
- Fixed-Dose Protocol
- Diazepam (Valium)
- Day 1: 15 to 20 mg orally four times daily
- Day 2: 10 to 20 mg orally four times daily
- Day 3: 5 to 15 mg orally four times daily
- Day 4: 10 mg orally four times daily
- Day 5: 5 mg orally four times daily
- Lorazepam (Ativan)
- Days 1-2: 2-4 mg orally four times daily
- Days 3-4: 1-2 mg orally four times daily
- Day 5: 1 mg orally twice daily
- Chlordiazepoxide (Librium)
- Day 1: 50-100 mg orally four times daily
- Days 2-4: 25-50 mg orally four times daily
- Decrease by 20% per day
- Diazepam (Valium)
XX. Management: Severe Alcohol Withdrawal Protocol (CIWA-Ar >20, with maximum score 67)
- Indicated in Delirium Tremens
- Disposition
- Inpatient Facility Intensive Care Unit
-
General Protocol (Requires ICU observation)
- Endpoint
- Until adequate sedation (RASS Score 0 to -2) and improved CIWA-Ar score OR
- Refractory to very high Benzodiazepine doses (e.g. Diazepam 200 to 500 mg cummulative total)
- Switch to refractory measures as below (e.g. Phenobarbital, Propofol)
- Diazepam (Valium)
- Start: 10-20 mg IV every 5-15 min prn
- Titrate dose for refractory symptoms
- Increase to 20 mg for 2 doses
- Increase to 40 mg for 2 doses
- May give 80 mg if no effect at 40 mg
- Lorazepam (Ativan)
- Start: 2-4 mg IV every 15-20 min prn
- Titrate dose for refractory symptoms to 4 mg, then 8 mg, then 16 mg, then 32 mg
- Chlordiazepoxide (Librium)
- Start: 25 to 100 mg IM/IV every 1-4 hours (max: 300 mg/day)
- Endpoint
- Defining Criteria and Additional Medication Indications
- Systolic Blood Pressure > 200 mmHg
- Diastolic Blood Pressure > 140 mmHg
- Heart Rate > 140
- Temperature > 38.3 C (101 F)
- Tremulousness, Insomnia, or Agitation
- Refractory or Adjunctive measures (may require Advanced Airway and Ventilatory support)
- Phenobarbital 10 mg/kg up to 130-260 mg IV prn
- Propofol induction (RSI), followed by intubation and Propofol infusion
- Dexmedetomidine (Precedex) 0.2 to 0.6 mcg/kg/hour up to 1.2 mg/kg/hour
- Do not reduce Benzodiazepine dose when used with Dexmedetomidine
- Ketamine (NMDA Antagonist)
- May reduce Benzodiazepine requirement in severe Alcohol withdawal (ICU patients)
- Ketamine 0.2 g/kg/hour infusion (avoid doses 0.3 to 1 g/kg/hour)
- Wong (2015) Ann Pharmacother 49(1):14-9 +PMID:25325907 [PubMed]
- Pizon (2018) Crit Care Med 46(8):e768-71 +PMID:29742583 [PubMed]
- Shah (2018) J Med Toxicol 14(3): 229-36 +PMID:29748926 [PubMed]
XXI. Management: Phenobarbital Single Agent Alcohol Withdrawal Protocol
- Indications
- Alcohol Withdrawal AND
- No Benzodiazepines or other sedating medications given AND
- No other active neurologic problems
- Precautions
- Do NOT combine with Benzodiazepines or other sedating medications (apnea risk!)
- Avoid in Hepatic Encephalopathy
- Dosing listed here is for adults only
- Protocol
- Continue protocol until patient is awake and calm
- IV Phenobarbital Load
- Phenobarbital 10 mg/kg IV Ideal Body Weight (IBW) over 30 minutes
- Wait 30 minutes before any additional Phenobarbital given
- Do not use loading dose if any other CNS Depressants have been given (e.g. Opioids, Benzodiazepines)
- IV Phenobarbital Titration
- Up to every 30 minutes give one of the 2 following doses as needed (no maximum, titrate to effect)
- Mild Symptoms: 130 mg IV over 3 minutes every 15 to 30 minutes as needed
- Severe symptoms 260 mg IV over 5 minutes every 30 minutes as needed
- Oral or IM Phenobarbital Maintenance (non-ED or ICU setting)
- Up to every 60 minutes give one of the 2 following doses as needed
- Mild Symptoms: 100 mg oral or IM every 60 minutes as needed
- Severe symptoms 200 mg oral or IM every 60 minutes as needed
- Maximum Cummulative Total Dose (Loading dose and any additional maintenance doses)
- Relative maximum cummulative total: 20 mg/kg Ideal Body Weight
- Absolute maximum cummulative total: 30 mg/kg Ideal Body Weight
- Efficacy
- Decreased hospital length of stay when compared with Benzodiazepines in withdrawal
XXII. Prevention
- See Alcohol Abuse Management
- Following Alcohol treatment program and aftercare are critical following Alcohol Withdrawal Protocol
XXIII. Resources: Patient Education
- Information from your Family Doctor: Alcohol Withdrawal
XXIV. 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
- Weingart (2024) Severe Alcohol Withdrawal, EM:Rap, 6/10/2024
- 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]