Elsevier Logo

ThisiscontentfromClinicalKey

Want more answers?

Sign up for your free ClinicalKey trial today!  Your first step in getting the right answers when you need them. ClinicalKey is a clinical knowledge solution designed to help healthcare professionals and students find the right answers by providing in-depth, evidence-based knowledge – all from one resource.

Mar.06.2020View related content

Alcohol withdrawal

Synopsis

Key Points

  • Alcohol withdrawal may occur after cessation or reduction of heavy and prolonged alcohol use; manifestations are characterized by autonomic hyperactivity and central nervous system excitation
  • Alcohol withdrawal can start as early as 6 hours from the last drink and early manifestations are characterized by sympathomimetic symptoms, tremor, anxiety, insomnia, nausea, and vomiting r1
  • Manifestations may worsen without treatment; progression to severe symptom manifestations including seizures and delirium tremens occurs in up to 5% of patients r2
  • Withdrawal is a clinical diagnosis and a diagnosis of exclusion; DSM-5 diagnostic criteria define the diagnosis r3
  • Ancillary testing does not usually aid in diagnosis; obtain routine baseline studies (eg, metabolic panel, liver function testing) to evaluate for concurrent problems in patients with moderate to severe withdrawal manifestations requiring admission
  • Obtain individualized studies based on presentation to identify concurrent conditions that may have contributed to precipitation of withdrawal
  • Outpatient alcohol withdrawal treatment with medical assistance may be used for select patients with mild to moderate withdrawal without significant comorbidity
  • Inpatient alcohol withdrawal treatment with medical assistance is required for patients with severe withdrawal and patients at risk for progression to severe withdrawal
  • Sedative hypnotics (ie, benzodiazepines) are the cornerstone of initial management
  • With effective treatment, progression of disease and development of delirium tremens may be avoided
  • Administer thiamine and folate supplementation in patients presenting in withdrawal; replenish potassium to correct hypokalemia r2
  • Refer all patients with alcohol withdrawal for alcohol use disorder treatment (eg, alcohol abstinence counseling, long-term rehabilitation)
  • Overall prognosis is best among patients without other acute medical problems
  • Morbidity and mortality are increased among patients with comorbidity, concurrent disease related to alcohol use disorder that complicates management,r4 and older ager5
  • Prevention of withdrawal may be possible with screening, early identification, and rehabilitation of patients with alcohol use disorder

Urgent Action

  • Early and aggressive treatment of alcohol withdrawal will halt progression to more severe forms of withdrawal
  • Treat moderate to severe withdrawal aggressively with rapid escalating doses of benzodiazepines initially
  • Seizures should be terminated with benzodiazepines (first line); second line agents include barbiturates and/or propofol
  • Wernicke encephalopathy requires urgent treatment doses of thiamine

Pitfalls

  • Patients may develop manifestations of withdrawal despite a detectable serum alcohol concentration
    • Consider diagnosis even in patients who are not abstinent from alcohol because a decreased amount of consumption can lead to withdrawal
    • Early and aggressive treatment of withdrawal manifestations is a key measure to diminish morbidity when indicated regardless of detectable blood alcohol concentration
  • Consider alcohol withdrawal diagnosis in patients admitted to hospital for other reasons if manifestations consistent with withdrawal develop
    • Up to 8% of patients admitted to hospitals with non–alcohol-related diagnoses exhibit signs of withdrawal r5
    • Early recognition and aggressive treatment decreases morbidity
  • Inadequate initial treatment of withdrawal symptoms may lead to worsening withdrawal
    • Treat aggressively to targeted treatment goals for sedation
  • Accurate diagnosis is key to appropriate management of manifestations
    • For example, benzodiazepines are the treatment of choice for alcoholic hallucinosis; administration of antipsychotics can be detrimental if hallucinations are considered attributable to a psychiatric illness rather than withdrawal
  • Acute illness may precipitate withdrawal episode
    • Maintain awareness for need to identify and treat any acute illness that occurs concurrent with withdrawal
  • Monitor for other coexistent conditions and alternate medical causes for patient decompensation or recalcitrant withdrawal r2
    • For example, persistent tachycardia may be a manifestation of alternate disease (eg, hypovolemia, sepsis, heart failure, thyrotoxicosis) rather than withdrawal alone
    • Failure to consider alternative and coexisting diagnosis may lead to increased morbidity and mortality
  • Subsequent episodes of alcohol withdrawal tend to increase in severity
    • Encourage treatment and counseling for alcohol use disorder after an episode of acute withdrawal to prevent recurrent withdrawal episodes
  • Prophylactic thiamine replacement is important to avoid increased risk of Wernicke encephalopathy r2
    • Maintain high suspicion for Wernicke encephalopathy in patients presenting with suspicious manifestations (eg, ataxia, ophthalmoplegia) because mortality is high and diagnosis is frequently missed
    • Treatment thiamine dosing is higher and longer than prophylactic dosing for patients presenting with concern for Wernicke encephalopathy
    • Administer thiamine before (preferred) or with glucose administration in patients at risk for Wernicke encephalopathy because supplemental administration of glucose alone can precipitate encephalopathy

Terminology

Clinical Clarification

  • Alcohol withdrawal may occur after cessation or reduction of heavy and prolonged alcohol use; manifestations are characterized by autonomic hyperactivity and central nervous system excitation r3r6
  • Severe symptom manifestations (eg, seizures, delirium tremens) may develop in up to 5% of patients r2

Classification

  • Based on severity
    • Minor alcohol withdrawal syndrome r1r4
      • Manifestations occur early, within the first 48 hours after last drink or decrease in consumption r7
        • Manifestations develop about 6 hours after last drink or decrease in consumption and usually peak about 24 to 36 hours; resolution occurs in 2 to 7 daysr8 if withdrawal does not progress to major alcohol withdrawal syndrome r1
      • Characterized by mild autonomic hyperactivity (eg, tachycardia, hypertension, diaphoresis, hyperreflexia), mild tremor, anxiety, irritability, sleep disturbances (eg, insomnia, vivid dreams), gastrointestinal symptoms (eg, anorexia, nausea, vomiting), headache, and craving alcohol r1
    • Major alcohol withdrawal syndrome r1r4
      • Progression and worsening of withdrawal manifestations, usually after about 24 hours from the onset of initial manifestations r1
        • Manifestations often peak around 50 hours before gradual resolution or may continue to progress to severe (complicated) withdrawal, particularly without treatment r1
      • Characterized by moderate to severe autonomic hyperactivity (eg, tachycardia, hypertension, diaphoresis, hyperreflexia, fever); marked tremor; pronounced anxiety, insomnia, or irritability; anorexia; decreased seizure threshold; hallucinations; and delirium r1
    • Complicated or severe alcohol withdrawal
      • Rigorous definition is lacking r9
      • Many experts define based on presence of any of the following:
        • Withdrawal seizures r2r9
        • Delirium tremens
        • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score greater than 20 r10
        • Major alcohol withdrawal syndrome manifestations refractory to high-dose benzodiazepines r9
      • May occur in up to 5% of patients r2r11
  • Based on progressive stages r4
    • Stage 1
      • Minor symptoms not usually associated with significantly abnormal vital signs r10
    • Stage 2
      • Mild to moderate symptoms associated with abnormal vital signs and possibly alcoholic hallucinosis r10
    • Stage 3
      • Mild to moderate symptoms associated with abnormal vital signs and development of seizures
    • Stage 4
      • Moderate to severe symptoms associated with abnormal vital signs, possibly seizures, and development of delirium r10

Diagnosis

Clinical Presentation

Characteristic withdrawal syndrome develops within hours to days after cessation or reduction of heavy and prolonged alcohol use r3

  • Probability of developing withdrawal rises with increasing quantity and frequency of alcohol consumption r3
    • Most affected patients are drinking daily for multiple days and consuming large amounts (ie, more than 8 drinks/day for multiple days) r3r9
  • Symptoms typically begin after sharp decline in blood alcohol concentration r3
  • Reduction or cessation in alcohol use may not always be intentional r4r12
    • Inability to acquire or pay for alcohol
    • Gastrointestinal illness characterized by decreased oral intake
    • Hospital admission for another medical issue r5
      • Up to 8% of patients admitted to hospitals with non–alcohol-related diagnoses exhibit signs of withdrawal

Earlier medical history may be significant for: r4

  • Alcohol use disorder c1
    • 50% to 80% of patients with alcohol use disorder develop some form of central nervous system stimulation and adrenergic hyperactivity with reduction or discontinuation of alcohol consumption r7r11
    • Suspect alcohol dependence in female patients who: r10
      • Consume more than 1 drink daily or more than 7 weekly
      • Have had more than 4 drinks on a single occasion in the past year (generally within 2 hours)r13
    • Suspect alcohol dependence in male patients who: r10
      • Consume more than 2 drinks daily or more than 14 drinks weekly
      • Have had more than 5 drinks on a single occasion in the past year (generally within 2 hours)r13
  • History of prior withdrawal
    • Course of prior alcohol withdrawal episodes is the most reliable predictor of subsequent episodes r14

Psychiatric history

  • Alcohol may cause several psychiatric conditions such as alcohol-induced mood, anxiety, or psychotic disorder r4
  • Underlying psychiatric disorders (eg, antisocial personality disorder, schizophrenia, major anxiety disorders, bipolar disorder) or other drug use disorder and dependence may be present

Factors that may modify withdrawal symptoms or course

  • Relief of symptoms can occur by administration of alcohol or benzodiazepines r3
  • Concurrent use of medication for other underlying disorders (eg, β-blockers, α₂-adrenergic agonists) may blunt typical abnormalities noted in vital signs at presentation r2

Presence of comorbidity

  • Patients with underlying psychiatric disorders may use alcohol to alleviate psychiatric symptoms such as anxiety and depression r4
  • Acute medical or surgical disorder may precipitate withdrawal r4
  • Poorly controlled medical comorbidity may precipitate withdrawal r4

Acute withdrawal may progress in stages ranging in severity from mild to severe r15

  • Manifestations during stages may overlap and may not progress in a precise sequential pattern r4
  • Early withdrawal: symptoms of central nervous system stimulation typically occurring within 48 hours of drinking cessation r7
    • Stage 1 (hangover stage)
      • Initial broad withdrawal manifestations begin 6 to 8 hours after last drink and may include: r2
        • Sympathomimetic symptoms (eg, diaphoresis, palpitations) c2c3
        • Mild tremor c4
        • Insomnia and anxiety c5c6
        • Gastrointestinal (eg, nausea, vomiting) c7c8
        • Headache c9
      • If withdrawal does not progress, these manifestations may resolve within 24 to 48 hours r2
    • Stage 2 (alcoholic hallucinosis stage)
      • Develops approximately 24 to 48 hours after last drink; may be up to 8 days r4
      • Worsening sympathomimetic symptoms (eg, diaphoresis, fever), marked tremors, worsening hyperactivity, and insomnia c10c11c12c13c14
      • Sensorium is lucid but nightmares or illusions are not uncommon c15c16
      • Hallucinations may develop
        • Most commonly occur 12 to 24 hours after last drink r2
        • Occur in 7% to 8% of untreated patients with withdrawal r2
        • Can be visual, auditory, or tactile r2
        • May occur in isolation without other broad withdrawal manifestations
        • Sensorium is normal (ie, delirium is absent; patient is aware that hallucinations are not real) r7
    • Stage 3 (tonic-clonic seizure stage)
      • Similar to stage 2 with development of tonic-clonic seizures r4c20c21c22c23c24
      • Withdrawal seizures (rum fits)
        • Commonly occur 12 to 48 hours after last drink r2
        • May occur in up to 10% of patients r6
          • Alcohol withdrawal represents 1 of the most common causes of adult-onset seizures r1c25
        • Commonly consist of isolated, short-duration, generalized tonic-clonic seizures with short or absent postictal period r6c26c27c28c29
          • May occur in clustersr17r4 and may be recurrent in a minority of patients r4r7
          • Prolonged seizures and status epilepticus are relatively uncommon r4c30c31
        • Seizures impart increased risk for complications (eg, aspiration pneumonia, rhabdomyolysis) r4
        • About one-third of patients who develop seizures progress to delirium tremens without treatment
  • Late withdrawal: symptoms typically occurring later than 48 hours after drinking cessation r7
    • Stage 4 (delirium tremens stage)
      • High likelihood that a concurrent, clinically relevant medical condition exists when delirium develops r3
        • May include liver failure, pneumonia, gastrointestinal bleeding, head trauma, hypoglycemia, electrolyte imbalance, and postoperative state
      • Delirium tremens
        • Consists of severe autonomic hyperactivity and ongoing agitation plus rapid-onset delirium (ie, fluctuating disturbance of attention and cognition)
          • Manifestations fluctuate in severity throughout the day and may include: r9
            • Lack of attention and awareness c32c33
            • Memory loss and disorientation c34c35
            • Hallucinations c36
            • Agitation r7c37
        • Usually begins 2 to 3 days after initial withdrawal symptoms appear and lasts for 1 to 8 days; may be delayed up to 12 days r2r4
          • Rarely, may develop as early as 8 hours after last drink r2
        • Often associated with cardiovascular, respiratory, and metabolic abnormalities r4
        • Occurs in 1% to 5% of hospitalized patients with withdrawal r2r4
        • Risk is significantly increased in patients with concurrent acute medical illness r4

Physical examination

  • Common findings r4r6
    • Autonomic hyperactivity with sympathomimetic signs
    • Central nervous system hyperstimulation
      • Coarse tremor c44
        • Often most easily found in the hands or tongue
      • Hyperreflexia c45
      • Hallucinations c46
      • Seizures c47
      • Delirium c48
  • Findings concerning for concurrent Wernicke encephalopathy
    • Nystagmus or oculomotor abnormalities c49c50
    • Ataxia or gait disturbance c51c52

Causes and Risk Factors

Causes

  • Underlying cause of alcohol withdrawal syndrome is multifactorial; undetermined genetic factors likely play a role
    • Long-term alcohol use causes a depressant effect on the central nervous system, leading to adaptive changes in neurotransmitter and receptor physiology r4
      • Central nervous system depression occurs with long-term alcohol use
        • Enhanced inhibitory tone occurs through GABA receptor modulation (affecting several proteins involved in γ-aminobutyric acid pathways) r2
        • Inhibited excitatory tone occurs through NMDA receptor modulation (affecting several proteins involved in N-methyl-D-aspartate pathways) r2
      • Alcohol administration increases catecholamine levels affecting central α- and β-adrenergic receptors r1r4
      • Alterations of balance in other neurochemical systems (eg, serotonin, endogenous opioid, nicotinic cholinergic, dopamine), electrolytes (eg, hypomagnesemia), and vitamin deficiencies (eg, thiamine) occur with long-term alcohol intake
    • Functional adaptations result in development of tolerance phenomenon in patients with alcohol use disorder
    • Kindling phenomenon c53
      • Refers to development of neuronal networks that may result in worsening episodes of withdrawal on subsequent episodes
  • Discontinuation or dramatic reduction in alcohol consumption c54
    • Central nervous system hyperstimulation results from loss of GABA receptor inhibition and potentiation of NMDA receptor excitation r2
    • Dopaminergic dysregulation may also play a role in agitation, hallucinations, and delirium r7
    • Gradual increase in adrenergic activity results from an excess glutamate activity on excitatory NMDA receptors and excess catecholamine effects on central α- and β-adrenergic receptors r1r4
    • Abnormalities in the balance of other neurochemical systems, electrolytes, and vitamins may also contribute to development of withdrawal

Risk factors and/or associations

Age
  • Risk of withdrawal increases with age r3
    • Most commonly in middle-aged adults r4c55
    • Relatively rare in patients younger than 30 years r3
  • Older patients are at increased risk for morbidity and mortality r5c56c57
Sex
  • Most patients admitted to hospitals with alcohol withdrawal syndrome are male r4c58c59
Other risk factors/associations
  • Risk factors for withdrawal
    • Risk increases linearly with quantity and frequency of alcohol intake r9c60
    • Concurrent medical condition that precludes alcohol intake r3
    • Family history of alcohol withdrawal r3c61
    • Personal history of alcohol withdrawal r3
    • Concurrent long-term use and then discontinuation of sedative, hypnotic, or anxiolytic drugs r3c62c63
    • Patients with tolerance phenomenon r7c64
  • Risk factors for severe withdrawal course are inconsistently reported in literature but may include:
    • Prior episode of withdrawal, especially severe withdrawal r17c65
    • Drinking patterns that include: r4
      • Greater maximum dose of daily alcohol
      • Greater number of drinking days per month
      • Need for alcoholic drink in the early morning
    • Older age, especially 60 years or older r3r18c66
    • Acute and chronic comorbid medical problems (eg, alcoholic liver disease, cointoxications, trauma, infections, sepsis, history of structural brain lesionr19) r4c67c68c69c70c71c72
    • Nonmedical use of sedative hypnotics r4c73
    • Detectable blood alcohol level on admission with withdrawal manifestations r4c74
    • Severe symptoms early in withdrawal course r7
    • Grade 2 severity or higher on presentation (initial Clinical Institute Withdrawal Assessment for Alcohol [Revised] score greater than 10) r4c75
    • Abnormal liver function (serum AST activity above 80 units/L) r4c76
    • Presence of significant dehydration or electrolyte abnormalities at presentation r15c77c78
    • Low initial platelet count and/or serum potassium level r14r19c79c80
    • Male sex r4
  • Risk factors for delirium tremens are inconsistently reported in literature but may include:
    • Concurrent medical illness (eg, pneumonia, active ischemia) r7c81c82
    • History of delirium tremens r11c83
    • Withdrawal seizures, specifically if left untreated or recurrent r7r11c84
    • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score of 15 or higher r11c85
    • Sustained drinking history r2c86
    • Systolic blood pressure above 150 mm Hg and/or heart rate above 100 beats per minute r11c87c88
    • Last alcohol intake greater than 2 days r2c89
    • Age older than 30 years r2c90
    • Recent misuse of other depressants (eg, benzodiazepines) r11c91c92

Diagnostic Procedures

Primary diagnostic tools

  • Withdrawal is a clinical diagnosis and a diagnosis of exclusion r2
    • DSM-5 diagnostic criteria define the diagnosis
    • Exclude alternate diagnoses that mimic withdrawal
    • Consider presence of concomitant condition (eg, comorbidities, complications of alcohol use disorder) that may have contributed to the withdrawal state by forcing abstinence
    • Consider risk of progression to severe withdrawal r15
  • Measure severity of withdrawal with applicable severity assessment tool
    • Several scales are available; most commonly used include:
      • Short Alcohol Withdrawal Scale r10
        • 10-item scale requiring patient participation; most common tool used for outpatients
      • Clinical Institute Withdrawal Assessment for Alcohol (Revised) scale r4r20
        • 10-item scale requiring patient cooperation; most common tool used for inpatients
      • Richmond Agitation-Sedation Scale r4r21
        • Reliable scale for patients requiring ICU care
    • Scales are not diagnostic tools; rather, scales objectively measure degree of withdrawal in a patient with clinical diagnosis of withdrawal r2r15
  • Evaluate for other disease that may have contributed to precipitation of withdrawal r2
    • Consider presence of concomitant condition or complication of long-term alcohol use, especially in the presence of severe withdrawal (eg, delirium) r3
      • Withdrawal is often precipitated in patients with comorbid medical or surgical conditions during periods of abstinence when illness or surgery prevents alcohol intake r4
      • Investigations may be necessary to exclude conditions such as pneumonia, sepsis, meningitis or encephalitis, pancreatitis, liver failure, gastrointestinal bleeding, head trauma, intracerebral hemorrhage, acute coronary syndrome, drug overdose, hypoglycemia, and electrolyte abnormalities
      • Guide additional diagnostic testing and work-up based on individual clinical presentation
    • Wernicke encephalopathy may present in association with withdrawal and triad of altered mental status, ophthalmoplegia, and ataxia
      • Full triad is present in only about one-third of patients and diagnosis is missed in up to 80% of cases r2
  • Obtain baseline admission studies for patients with moderate to severe alcohol withdrawal syndrome based on individual presentation (routine laboratory testing is not necessary for most patients with mild withdrawal) r4r10
    • Obtain finger stick glucose measurement for all patients with altered mental status or seizures r17
    • Most experts order the following:
      • Metabolic panel with serum electrolyte, magnesium, phosphate, and glucose levels, plus renal function testing r17
      • CBC r17
      • Liver function tests, including INR and serum AST, ALT, bilirubin, and ammonia r17
    • Consider the following:
      • Head CT or other brain imaging for patients with seizures r15
      • Blood alcohol concentration and urine drug screen
      • Serum calcium, phosphate, lipase, and creatinine kinase levels
      • Chest radiograph
      • ECG, cardiac biomarkers, and echocardiogram
      • Urinalysis
      • Arterial blood gas analysis
      • Blood, urine, and sputum cultures
      • Lumbar puncture with studies to assess for central nervous system infection in patients presenting with fever and mental status changes
      • Pregnancy test for premenopausal women
  • Refer to regionally specified protocols to guide evaluation strategy r22

Laboratory c93c94c95c96c97c98c99c100c101c102c103c104

  • Serum blood alcohol concentration c105
    • Serum blood alcohol concentration may assist in determining likelihood of withdrawal
      • High likelihood of withdrawal exists after prolonged heavy alcohol consumption when early manifestations (eg, autonomic hyperactivity) appear in the context of a moderately high but falling alcohol level r3
      • Anticipate worsening of withdrawal manifestations as ethanol concentration falls in patients presenting with alcohol withdrawal and an elevated ethanol concentration r2
  • Metabolic panel with serum electrolyte (including magnesium) and glucose levels r23c106c107c108c109
    • Abnormal findings are common in long-term alcohol use and may include: r24
      • Hypoglycemia
      • Hypokalemia
      • Hypomagnesemia
      • Hypophosphatemia
  • Renal function tests (BUN, creatinine) c110c111
    • Renal insufficiency can guide choice of doses in treatment r25
  • Liver function testing c112
    • Evaluation of hepatic transaminases and synthetic liver function (eg, prothrombin time, INR) may help guide medication choice and assess for alcohol-related hepatic injury r25

Imaging

  • Head CT c113
    • May be indicated to exclude alternate causes of manifestations or with concern for trauma
  • Chest radiograph c114c115
    • May be indicated to assess for acute pneumonia or other concurrent pulmonary disease

Other diagnostic tools

  • DSM-5 clinical diagnostic criteria
    • Alcohol withdrawal syndrome r3c116
      • A: cessation of (or reduction in) alcohol use that has been heavy and prolonged
      • B: 2 (or more) of the following, developing within several hours to a few days after the cessation of (or reduction in) alcohol use described in criterion A:
        • Autonomic hyperactivity (eg, sweating, pulse greater than 100 beats per minute)
        • Increased hand tremor
        • Insomnia
        • Transient visual, tactile, or auditory hallucinations or illusions
        • Psychomotor agitation
        • Anxiety
        • Generalized tonic-clonic seizures
      • C: the signs and symptoms in criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
      • D: the signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance
    • Substance withdrawal delirium r26
      • Substance withdrawal delirium diagnosis should be made instead of substance withdrawal when symptoms in criteria A and C predominate in the clinical picture and when they are sufficiently severe to warrant clinical attention
      • Delirium criteria
        • A: disturbance in attention (ie, reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment)
        • B: disturbance develops over a short period (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during course of day
        • C: additional disturbance in cognition (eg, memory deficit, disorientation, language, visuospatial ability, or perception)
        • D: the disturbance in A and C are not better explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in the context of reduced level of arousal (eg, coma)
        • E: there is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (ie, due to drug use disorder or medication), or exposure to a toxin, or is due to multiple causes
  • Short Alcohol Withdrawal Scale c117
    • Validated for use in outpatient setting r10
      • Symptoms that are scored include anxiety, confusion, restlessness, feeling miserable, memory issues, tremors (shakes), nausea, heart pounding, sleep disturbance, and sweating in the past 24 hours
      • Score is based on presence and severity of each symptom
        • None: 0 points
        • Mild: 1 point
        • Moderate: 2 points
        • Severe: 3 points
      • Mild withdrawal: score less than 12 points
      • Moderate to severe: score of 12 points or higher
  • Clinical Institute Withdrawal Assessment for Alcohol (Revised) r20c118
    • Objectively measures severity of withdrawal and determines likelihood of progressing alcohol withdrawal syndrome; clinical uses may include: r4
      • Determination of need for medically supervised withdrawal management
        • An initial score of greater than 10 is correlated with risk of developing severe withdrawal; requires further evaluation and development of admission goals of therapy r4
      • Monitor course of withdrawal and guide symptom-triggered treatment when alcohol use history is known
        • Patients with score less than 10 do not usually need additional medication r10
        • Patients requiring treatment with scores of 15 or less likely respond to moderate benzodiazepine doses r11
        • Patients with scores higher than 15 require close monitoring and aggressive treatment to avoid seizures and alcohol withdrawal delirium r11
    • Score is based on symptoms including nausea/vomiting, tremors, paroxysmal sweating, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache/head fullness, and orientation/clouding of sensorium r2
    • Scores are altered by pain, other medical and surgical issues, and administration of sedation agents r4
    • Scoring-based severity is variably reported and not rigorously standardized; refer to regional protocol to guide symptom-triggered treatment based on specific score
      • One source suggests the following: r10
        • Absent or very mild withdrawal: score of 8 or lower
        • Mild withdrawal: score of 9 to 14
        • Moderate withdrawal: score of 15 to 20
        • Severe withdrawal: score of 21 to 67
      • Other sources suggest the following levels of severity based on score
        • Absent, minimal, or mild: 9 or less,r27less than 8,r110 to 8r15
        • Moderate: 10 to 18,r278 to 15,r119 to 15r15
        • Severe: 19 or higher,r27higher than 15,r1116 or higherr15
  • Richmond Agitation-Sedation Scale r4r21c119c120c121
    • Use to assess effectiveness of sedation in patients who lack the ability to cooperate (eg, heavily sedated, intubated, combative)
    • Score is based on overall patient responsiveness and general level of sedation
      • +4: patient is combative; immediate danger to staff
      • +3: patient is very agitated; aggressive toward staff, removes catheters/tubes
      • +2: patient is agitated; patient-ventilator dyssynchrony, persistent nonpurposeful movement
      • +1: patient is restless; movements are not aggressive or vigorous, anxious or apprehensive mood
      • 0: patient is calm and alert
      • −1: patient is drowsy; awakening to voice, with eye contact, for periods of 10 seconds or more
      • −2: patient is lightly sedated; awakens to voice, with eye contact, for brief periods (less than 10 seconds)
      • −3: patient is moderately sedated; movement in response to voice, without eye contact
      • −4: patient is deeply sedated; movement in response to physical stimulation, but does not respond to voice
      • −5: patient is unarousable; does not respond to physical stimulation or voice
    • Goal is score of 0 to −2 (patient is in a calm, arousable state) r2

Differential Diagnosis

Most common

  • Sedative-hypnotic medication withdrawal r28r29c122
    • Withdrawal from chronically used sedative-hypnotic medications, including benzodiazepines, barbiturates, baclofen, or γ-hydroxybutyrate (GHB) r30r31
    • May present with symptoms similar to those of alcohol withdrawal syndrome such as anxiety, restlessness, tremor, tachycardia, delirium, hallucinations, and seizures
    • Sedative-hypnotic medication withdrawal and alcohol withdrawal are virtually indistinguishable from a clinical standpoint
    • History of long-term alcohol use may point toward a diagnosis of alcohol withdrawal or mixed withdrawal syndrome
    • Laboratory testing for potential drug use and blood alcohol concentration may help narrow specific cause of manifestations; review of state prescription drug database may reveal fulfillment of benzodiazepine prescriptions
  • Stimulant intoxication r32c123d1
    • Intoxication with substances such as cocaine, methamphetamine, amphetamine, and synthetic cathinones (eg, bath salts) can present similarly to alcohol withdrawal with agitation, tremor, sympathomimetic hyperactivity, and occasionally hallucinations and/or seizures
    • Clinical differentiation may be difficult; however, patients with stimulant intoxication characteristically exhibit stereotyped behaviors such as picking at objects (real or imagined) on the skin or bed sheets and paranoid behavior
    • Mydriasis is more consistently present and pronounced in patients with stimulant intoxication than with alcohol withdrawal
    • Laboratory testing for potential drug use and blood alcohol concentration may help narrow specific cause of manifestations; caveat: most synthetic cathinones are not detectable on standard drug testing
  • Schizophrenia r33c124d2
    • Chronic psychiatric disorder characterized by faulty perceptions and withdrawal from reality that may present similarly to alcohol withdrawal with delusions and hallucinations
    • Onset of schizophrenia is typically in adolescence or young adulthood and may be more gradual than onset of alcohol withdrawal syndrome
      • While substance use is common among schizophrenic patients, a history of long-term alcohol use would be present in patients with alcohol withdrawal syndrome
    • Delusions, movement disorders, and paranoia are common in patients with schizophrenia
    • Signs such as tremors and tachycardia may not be present in schizophrenia; sustained sympathomimetic findings should not be present in patients with schizophrenia
    • Schizophrenia is a clinical diagnosis based on DSM-5 criteria r34
  • Encephalitis r35c125d3
    • Rapid onset of inflammation of the brain usually caused by an infectious or autoimmune process
    • Presents similarly with hallucinations, delirium, tremors, and/or seizures
    • Signs of inflammation (eg, fever) are common
    • While historical features can usually be used to differentiate between encephalitis and alcohol withdrawal, objective testing may be necessary
    • MRI of the brain, lumbar puncture with cerebrospinal fluid analysis, and/or continuous EEG monitoring can aid in diagnosis
  • Hepatic encephalopathy r4c126d4
    • Encephalopathy associated with chronic liver dysfunction characterized by delirium and asterixis
    • May present similarly with seizures and altered sensorium
    • Other stigmata of chronic liver disease (eg, jaundice, scleral icterus, coagulopathy, caput medusa) may be present
    • In contrast to alcohol withdrawal syndrome, hepatic encephalopathy is typically associated with central nervous system depression and asterixis, as opposed to coarse tremor and central nervous system excitation
    • Elevated serum ammonia level can assist in differentiating from alcohol withdrawal syndrome
  • Thyrotoxicosis r36c127d5
    • Caused by exposure to excess circulating thyroid hormones
    • Similar manifestations include restlessness, tremors, palpitations, tachycardia, and hypertension
    • History of long-term alcohol use and recent cessation or reduction of alcohol use can differentiate alcohol withdrawal syndrome from thyrotoxicosis
    • Physical examination findings such as thyromegaly and/or exophthalmos are sometimes seen in hyperthyroidism but will be absent in alcohol withdrawal syndrome
    • Laboratory testing can be used if history is not sufficient to differentiate cause of patient's presentation
      • Low or nondetectable TSH level and elevated thyroid hormone levels will be present in thyrotoxicosis
  • Epilepsy r37c128d6
    • Often idiopathic or related to a previous medical cause, an underlying chronic seizure disorder may be mistaken for alcohol withdrawal syndrome
    • If seizures are generalized and tonic-clonic, they will appear similar to alcohol withdrawal seizures
    • History of recurrent seizures or long-term anticonvulsant use is more commonly associated with epilepsy
      • Status epilepticus may occur as part of alcohol withdrawal syndrome but is relatively uncommon
    • Thorough medication and alcohol use histories can differentiate these diagnoses
    • Diagnosis is clinical and usually based on occurrence of at least 2 unprovoked seizures occurring more than 24 hours apart; central nervous system imaging and EEG may aid in diagnosis
  • Cranial trauma r38r39c129
    • Patients with cranial trauma may have confusion, altered mental status, and seizures; physical signs of trauma to the head and neck may be present
    • Patients with alcohol use disorder are at increased risk of trauma
    • Cranial trauma presentation usually does not include other signs seen in alcohol withdrawal syndrome (such as tremors)
    • History of long-term alcohol use, as opposed to acute alcohol intoxication, can help differentiate between these entities
    • If significant cranial trauma is suspected, obtain CT scan of brain (without contrast material) to evaluate for fractures or intracranial hemorrhage
  • ICU delirium r40c130
    • Delirium is a generic syndrome with many causes; delirium seen in the ICU setting is associated with critical illness and often respiratory failure
    • Both ICU delirium and delirium tremens present with alterations in sensorium and can occur after admission to ICU setting
    • ICU delirium will typically occur in older adults with critical illness and is associated with more adverse prognosis
    • While delirium tremens presents with a hyperactive delirium, ICU delirium will typically be of a mixed or hypoactive subtype r4
    • Diagnosis of delirium is clinical and based on DSM-5 diagnostic criteria r41

Treatment

Goals

  • Monitor withdrawal course and provide symptomatic treatment with aim to normalize vital signs, relieve anxiety, and halt progression to severe withdrawal r6
  • Manage severe withdrawal (eg, seizures, delirium) and monitor for complications (eg, respiratory depression, pneumonia, rhabdomyolysis) r6
  • Address and manage other comorbid or concurrent medical, surgical, traumatic, toxicologic, or psychiatric issues r4
  • Arrange for substance use disorder treatment and encourage long-term abstinence r6

Disposition

General criteria for outpatient management r10

  • Mild to moderate withdrawal and:
    • No serious psychiatric problems (ie, suicidal ideation, psychosis), medical comorbidity, or acute illness
    • No significant laboratory abnormalities, when obtained
    • No concurrent substance use disorder
    • Low risk for development of delirium tremens
    • No history of significant alcohol withdrawal (eg, withdrawal seizure)
    • Patient ability to take oral medications
    • Patient commitment to frequent follow-up visits
    • Patient with friend or relative who can monitor patient and administer medications
    • Age 16 years or older r22

General criteria for discharge with referral for outpatient alcohol dependence treatment program

  • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score less than 8 to 10 r2r4r42
  • Patient not currently intoxicated (alcohol or other drugs) r2
  • No history of complicated alcohol withdrawal syndrome (ie, seizures, hallucinosis, delirium tremens) r2
  • No significant medical or psychiatric comorbidity or suicidal ideation r2r42
  • Patient ability to maintain regular outpatient visits and therapy r2

General criteria for outpatient detoxification

  • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score 15 or less r2
  • No symptoms or history of delirium tremens or alcohol withdrawal seizures r2r42
  • Ability to take oral medications r2
  • Presence of a family member or close contact who can stay with the patient r2
  • Lack of unstable medical condition r2
  • No psychosis or suicidality r2
  • Ability to commit to daily medical visits and adequate follow-up r2

Admission criteria

Admission criteria to medical unit or inpatient medically supervised detoxification center r4

  • Patients with more than mild alcohol withdrawal plus all of the following:
    • No underlying medical or surgical condition requiring ICU-level care r2
    • Normalization or near-normalization of vital signs within emergency department r2
    • Clear sensorium r2
    • Responsive to 10 to 20 mg diazepam and tolerating 2 to 4 hours between benzodiazepine doses r2
  • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score higher than 15 r42
  • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score 8 to 15 and a history of delirium tremens or alcohol withdrawal seizures r42
  • Patients at high risk for progression to worsening stage of withdrawal (ie, mild withdrawal despite a detectable ethanol concentration, concomitant use of benzodiazepines, history of severe withdrawalr17)
  • Patients with concomitant major electrolyte disorder, decompensated medical illness,r42 psychiatric illness, or pregnancy r17
  • Presence of medical or psychiatric condition or suicidal ideation requiring inpatient admission r2
Criteria for ICU admission
  • Intubation or other respiratory support requirement r4
  • Severe hemodynamic abnormalities r4
    • Significant tachycardia or hypotension
  • Persistent fever higher than 39°C r4
  • Severe, or advanced stage 2 or greater, withdrawalr4
    • Delirium
    • Recurrent seizures
    • Requirement for large or escalating doses of benzodiazepines or barbiturates r2r6
    • Moderate to severe withdrawal despite elevated blood alcohol concentration r2
  • Consider for patients with:
    • Significant medical or surgical comorbidities (eg, cardiac disease, respiratory disease, renal insufficiency, acute serious infection, trauma) r2r4
    • Evidence of significant alcohol-related complications (eg, hepatic insufficiency, pancreatitis, gastrointestinal bleeding, rhabdomyolysis) r2
    • History of complicated alcohol withdrawal or severe withdrawal course r2
    • Marked fluid or electrolyte abnormalities r4
    • Patients requiring treatment of suspected Wernicke encephalopathy r2
    • Older age r17

Recommendations for specialist referral

  • Treatment of severe withdrawal or patients at high risk for severe withdrawal (eg, comorbidity, concurrent acute illness) should be managed by a clinician well trained in management of alcohol withdrawal syndrome (eg, addiction medicine specialist) r7r11
  • Consult a medical toxicologist or addiction medicine specialist for patients with benzodiazepine-resistant withdrawal and severe withdrawal for further diagnostic and treatment recommendations

Treatment Options

Resuscitation and stabilization is first aspect of care while assessing need for treatment of concurrent medical conditions r2

  • Manage airway and administer oxygen as indicated clinically r17
  • Initiate fluid resuscitation and start IV fluids when clinically indicated r17
  • Treat concurrent medical conditions r17
  • Treat hypoglycemia; begin thiamine administration before glucose (preferred) r9

Determine level of care and setting necessary for appropriate management

  • Patients with very mild withdrawal (ie, Clinical Institute Withdrawal Assessment for Alcohol [Revised] score of less than 8-10 with isolated stage 1) do not require pharmacologic management or admission if there is no progression or complicating factors r4r11
    • Some experts consider prescribing brief lorazepam regimen (2-4 mg every 4 hours) as needed for 3 to 5 days r42
  • Patients with mild to moderate manifestations without significant comorbidity or significant risk of developing severe withdrawal may be managed in either: r4r10r18
    • Outpatient setting with oral medications and daily follow-up when environment is conducive for recovery
    • Residential detoxification centers when home environment is unstable or not conducive for recovery
      • Centers may be medically managed by nursing staff with consulting physician or nonclinically managed by social workers and counselors
  • Stabilization in an emergency setting and medically monitored inpatient or residential admission is appropriate for patients presenting with: r10
    • Moderate to severe manifestations r4
    • Significant comorbid psychiatric, medical, or surgical conditions r4
    • Patients at risk for severe withdrawal r18

Regional protocols are available to guide management strategy for both inpatient and outpatient treatment r22

Standard inpatient alcohol withdrawal treatment with medical assistance r6

  • Sedative hypnotics are the cornerstone of initial management r9
    • Goal of initial treatment is rapid sedation with normalization of vital signs r6
      • Consider alternative or concurrent diagnosis if appropriate sedation is achieved without normalization of vital signs r17
      • Appropriately sedated patient is calm and sleepy but arousable without active hallucinations or seizures r21
      • Early and adequate treatment minimizes morbidity; administration of adequate benzodiazepine dose based on high withdrawal score (Clinical Institute Withdrawal Assessment for Alcohol [Revised]) is indicated regardless of blood alcohol concentration
    • Benzodiazepines are first line treatment r37r43
      • Treat psychomotor agitation and prevent progression to more serious withdrawal symptoms (eg, seizures, delirium tremens)
      • Act as GABA-A agonist to overcome loss of central nervous system GABA-A inhibitory effects r2
      • Preferred methods of administration include:
        • IV route for severe symptoms; oral route for less severe symptoms r2
        • Front-loading (loading dose) of benzodiazepines r44
          • Decreases rate of seizures, achieves earlier symptom control, and decreases total cumulative dose of medication needed
          • Involves high initial doses repeated frequently (eg, every 2-3 hours)
          • Often a long-acting agent is used (eg, diazepam)
        • Rapid and repeated escalating dosing (ie, double subsequent doses if control not achieved) of benzodiazepines
          • Reduces risk of seizures, delirium tremens, and need for mechanical ventilation in patients with severe withdrawal r2
          • Titrate based on sequential sedation scale scores r4
          • No maximum dose of benzodiazepines exists for treatment of alcohol withdrawal r2
          • Dose required to control manifestations is highly variable among patients r11
      • Debate exists regarding which benzodiazepine is the best treatment option r2
        • Some clinicians prefer IV diazepam or lorazepam for acute severe symptom control r2
          • Diazepam has shorter onset of action when compared with lorazepam, which may allow more rapid determination of dose response and more frequent dose titration r9
          • Longer duration of diazepam compared with lorazepam may allow for smoother downward titration r9
          • Diazepam may require dose adjustment in patients with renal failure because active metabolites are eliminated by kidneys; avoid in patients with liver disease r9
          • Lorazepam may be safer in patients with liver dysfunction and those at high risk of serious medical consequences after sedation (eg, elderly patients, those with severe pulmonary dysfunction) because lack of active metabolites leads to lower risk of overdose r7
        • Exercise caution with routine use of more than 1 type of benzodiazepine in combination; experts recommend use of only a single benzodiazepine r7
          • Use of 2 different benzodiazepines may be required in select scenarios including: r45
            • Transitioning to tapering phase of treatment
            • Initial stabilization phase of treatment, particularly in patients with severe withdrawal
              • Some experts maintain that alternating doses of lorazepam and diazepam in patients with severe withdrawal may be more effective at arresting withdrawal than use of lorazepam alone and leads to less postwithdrawal sedation than use of diazepam alone
      • Benzodiazepine equivalents: diazepam 5 mg = lorazepam 1 mg = chlordiazepoxide 25 mg = oxazepam 15 mg r15
    • Second line adjunct treatments for withdrawal resistant to benzodiazepines alone include phenobarbital and/or propofol r2
      • Can work synergistically with benzodiazepines on the GABA-A receptor r6r46
        • Limited data suggest that a single dose of IV phenobarbital combined with symptom-triggered benzodiazepine treatment of acute withdrawal decreases rates of ICU admission without significant adverse effects r47
      • Respiratory and cardiac depressant effects are more common than with benzodiazepines alone
      • Emerging adjunct treatments include dexmedetomidine and ketamine r2
  • Continued inpatient alcohol withdrawal management with medical assistance
    • Dosing regimens
      • Symptom-triggered (as needed) dosing of benzodiazepines is preferred to scheduled dosing after initial stabilization of symptoms for most inpatients r44
        • Symptom-triggered dosing based on severity scales allows for individualized dosing and results in shorter duration of therapy and lower cumulative medication doses r2r9
        • Numerous regional guidelines exist outlining individual treatment protocols, with a great deal of variability among them; insufficient evidence is available to recommend one individual protocol above another
          • Refer to individual hospital-driven and regional protocols for specific dosing recommendations r7r17
          • Widely used regimen is available r48
      • Fixed-tapering-dose regimen may be best suited for outpatient detoxification and for patients in whom sedation scales cannot be accurately applied (eg, severe comorbid illness)
    • Use objective measurement of symptom severity to determine frequency of administration targeted to treatment goals r2
      • Several scales assess severity of withdrawal
        • General target treatment goals include prevention of withdrawal seizures and delirium tremens, normalization of vital signs, and reduction or elimination of sensory disturbances (eg, agitation, anxiety, hallucinations)
        • Clinical Institute Withdrawal Assessment for Alcohol (Revised) is most commonly used r2
          • Goal of treatment is a calm awake state r15
          • Suggested treatment response to score r7
            • Less than 10: no need for pharmacotherapy
            • 11 to 20: clinical judgment is necessary regarding need for pharmacotherapy
            • Greater than 21: requires pharmacotherapy
          • Not validated for patients requiring ICU level of care r9
        • ICU sedation scales are often used for patients with severe withdrawal or withdrawal requiring intubation r2
          • Richmond Agitation-Sedation Score is most commonly used r4
            • Score of 0 to −2 indicates patient is in a calm, arousable state r2
    • Tapering
      • Usually benzodiazepines can be tapered down from peak dosing after about 48 to 72 hours r7
      • General guideline is to taper by about 20% of total daily benzodiazepine equivalent dose r45
      • Some experts prefer chlordiazepoxide for scheduled tapering protocol; other experts prefer lorazepam given by a symptom-triggered tapering strategy r45
  • Manifestation-specific treatment
    • Seizures
      • Benzodiazepines are first line treatment r2
      • Barbiturates and propofol are second line treatment options for seizures recalcitrant to benzodiazepines
      • Avoid other anticonvulsants (eg, carbamazepine, phenytoin, valproic acid, levetiracetam) for treatment or prophylaxis of seizures because most seizures are self-limited and inconsistently responsive to anticonvulsants other than benzodiazepines and barbiturates r2
      • Long-term anticonvulsant therapy is not necessary unless patient has underlying seizure disorder or epilepsy r4
      • Refractory status epilepticus may require management in consultation with specialists (eg, medical toxicologist, neurologist) and infusion of phenobarbital, pentobarbital, propofol, or midazolam r1
    • Alcoholic hallucinosis
      • Benzodiazepines are first line treatment r2
      • Avoid routine use of antipsychotics (eg, phenothiazines, butyrophenones) because they lower seizure threshold, often have anticholinergic effects (worsening hypertension, tachycardia, etc.), mask symptoms of worsening withdrawal,r17 and increase risk of respiratory complications r2r4
        • May be beneficial for patients with known or suspected thought disorders (eg, schizophrenia) r2
        • May be used in outpatient setting to diminish craving
    • Autonomic hyperactivity
      • Adjunct medications that may be useful to diminish symptoms but do not prevent seizures or delirium tremens include: r4
        • β-blockers
          • May diminish symptoms such as tremor, tachycardia, cardiac arrhythmias, hypertension, and craving
        • Clonidine (α₂ agonist)
          • May diminish severity of symptoms in mild to moderate withdrawal
    • Delirium and severe agitation
      • Management requires aggressive sedation r4
        • Extremely high benzodiazepine dosing may be required to achieve sedation goals
        • Titrated IV infusion may be required
        • Adjunct measures for benzodiazepine-resistant withdrawal may be required
      • Potential need for endotracheal intubation and mechanical ventilation is high r4
      • Maintain high awareness for potential complications such as development of pneumonia and sepsis r4
      • Physical restraints may be temporarily required; however, take care to avoid prolonged physical restraints without appropriate sedation owing to increased risk for rhabdomyolysis r6r15
      • Intermittent verbal reorientation to time, place, and date are important after stabilization r9
  • Benzodiazepine-resistant withdrawal
    • Clear definition is lacking; many experts define as lack of symptom control after the following doses:
      • At least 40 to 50 mg diazepam or 8 to 10 mg lorazepam within the first hour of treatment r2r9
      • More than 200 mg diazepam or 40 mg lorazepam within 3 hours of treatment r2
    • If rapid escalation of benzodiazepines fails to control symptoms, adjunct treatment options include phenobarbital, propofol, ketamine, and dexmedetomidine r2
      • Dexmedetomidine and ketamine use has not been studied as much as phenobarbital and propofol use r2
    • Consider alternative or concurrent diagnosis r17
    • Refractory withdrawal and delirium tremens may require intubation and mechanical ventilation r2
    • Most experts do not recommend treating with ethanolr17 or baclofen (selective GABA-B receptor agonist) r2
  • Treat concurrent acute illness and comorbid conditions in standard manner
    • May include treatment of other pathologic processes leading to alcohol withdrawal such as: r2
      • Infection (eg, pneumonia, sepsis, meningitis/encephalitis)
      • Gastrointestinal disease (eg, pancreatitis, hepatitis, alcoholic gastritis, bleeding esophageal varices)
      • Trauma (eg, head trauma)
      • Metabolic derangements (eg, hypoglycemia, electrolyte abnormalities)
      • Intracerebral hemorrhage
      • Acute coronary syndrome
      • Drug overdose

Outpatient alcohol withdrawal treatment with medical assistance

  • Aggressive counseling and rehabilitation are essential adjuncts to medication-assisted withdrawal to sustain recovery process and prevent relapse and subsequent episodes of withdrawal
  • Options include oral benzodiazepines, anticonvulsants,r2 β-blockers, and α₂-adrenergic agonists r10
    • Benzodiazepines
      • Choice of specific benzodiazepine
        • Long-acting benzodiazepines (eg, diazepam, chlordiazepoxide) are preferred in most patients r10
        • Intermediate-acting benzodiazepines (eg, lorazepam, oxazepam) are also effective and preferred in patients with liver dysfunction owing to lack of active metabolites r10
        • Chlordiazepoxide and oxazepam have less misuse potential than diazepam and lorazepam and may be preferred in patients at high risk for substance use disorders r10
      • Stress importance of abstinence from alcohol intake during treatment with benzodiazepine r10
        • Increased risk of respiratory depression and death is associated with alcohol and benzodiazepine coingestion
      • Administration technique
        • Either fixed-dose or symptom-triggered schedule may be used r10
          • Administration of dose during symptom-triggered management should be given for: r10
            • Short Alcohol Withdrawal Score of 12 or higher, or
            • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score higher than 9
        • Front-loading (loading dose) is not routinely recommended r10
      • Tapering
        • In general, doses can be gradually tapered down when Clinical Institute Withdrawal Assessment for Alcohol (Revised) score is less than 10 or Short Alcohol Withdrawal Score is less than 12 until eventual discontinuation r10
        • Symptoms usually resolve by day 7 following last alcohol use r10
    • Anticonvulsants
      • Data are limited;r49carbamazepine, valproic acid, and gabapentin may be used to reduce craving and prevent early relapser10
      • Anticonvulsants do not prevent withdrawal seizures or delirium tremens r10
    • β-blockers and α₂-adrenergic agonists
      • Atenolol and clonidine may be used as adjunct medications in combination with benzodiazepines to reduce adrenergic symptoms r10
      • β-blockers and α₂-adrenergic agonists do not prevent withdrawal seizures or delirium tremens

Counseling and rehabilitation

  • Cornerstone to recovery and adjunct to medication-assisted withdrawal
  • Refer all patients with alcohol withdrawal for alcohol use disorder treatment (eg, alcohol abstinence counseling, long-term rehabilitation) r4
  • American Society of Addiction Medicine placement criteria can guide placement after detoxification process r17r50
  • Provide patient with resources for assistance in long-term abstinence such as:
    • Alcoholics Anonymous r51
    • National Council on Alcoholism and Drug Dependence r52
    • National Institute on Alcohol Abuse and Alcoholism r53
    • Substance Abuse and Mental Health Services Administration r54r55

Drug therapy

  • Benzodiazepines r6
    • Diazepam c131
      • Rapid onset of action allows for ease of titration with less risk of dose stacking than with lorazepam r2
      • Active metabolites result in a longer duration of action compared with lorazepam r2
      • Readminister drug in an escalating dose fashion every 5 to 10 minutes until sedation goals and normalized vital signs are achieved r2
        • Common escalating dosing pattern for diazepam: r2
          • Initial dose is 10 mg, then observe for 5 to 10 minutes for clinical effects
          • When required, administer second dose of 20 mg then observe for 5 to 10 minutes for effects
          • When required, administer third dose of 40 mg then observe for 5 to 10 minutes for effects
          • Extremely high doses may be required for management of manifestations
            • Requirement of up to 500 mg for initial front-loading dose and cumulative dose of up to 2000 mg over 48 hours are reported r2
      • Can be administered intravenously, orally, or rectally
        • Diazepam Solution for injection; Adults: 10 mg IV initially, followed by 5 to 10 mg IV every 3 to 4 hours PRN. Doses of 5 to 10 mg IV may be given every hour if required. Hold if sedated.
      • Example of outpatient oral diazepam dosing regimens r10
        • Fixed-schedule
          • Diazepam Oral tablet; Adults: Day 1: 10 mg PO every 6 hours; Day 2: 10 mg PO every 8 hours; Day 3: 10 mg PO every 12 hours; Day 4 and 5: 10 mg PO at bedtime.
        • Symptom-triggered schedule
          • Diazepam Oral tablet; Adults: Day 1:10 mg PO every 4 hours PRN; Day 2 and 3: 10 mg PO every 6 hours PRN; day 4 and 5: 10 mg PO every 12 hours PRN.
    • Lorazepam c132
      • Slower time to peak effect than diazepam; therefore, dose stacking may occur if re-dosed before peak effect
      • Lack of active metabolites results in shorter half-life compared with diazepam r2
      • Less liver metabolism than other benzodiazepine options; may be preferred in patients with liver failure
      • Readminister drug in an escalating dose fashion every 15 to 20 minutes until sedation goals and normalized vital signs are achieved r2
        • Common escalating dosing pattern: r2
          • Initial dose is 4 mg, then observe for 15 to 20 minutes for effects
          • When required, administer second dose of 8 mg then observe for 15 to 20 minutes for effects
          • When required, administer third dose of 16 mg then observe for 15 to 20 minutes for effects
          • Extremely high doses may be required for management of manifestations
      • Can be administered intravenously, intramuscularly, or orally
        • Bolus dosing
          • Lorazepam Solution for injection; Adults: Initially 1—2 mg PO/IM/IV q8h. Titrate for desired clinical response. MAX: 4 mg/dose. NOTE: Dosing is highly variable; some patients require high doses of benzodiazepines to treat acute ethanol withdrawal.
        • Continuous infusion
          • For use in patients requiring frequent treatment
          • Infusion carries risk of propylene glycol toxicity and excessive accumulation of drug (ie, dose stacking)
          • Lorazepam Solution for injection; Adults: 1 to 4 mg/hour continuous IV infusion; titrate to effect. Max: 14 mg/hour. r56
      • Example of outpatient oral lorazepam dosing regimens r10
        • Fixed-schedule
          • Lorazepam Oral tablet; Adults: Day 1 and 2: 2 mg PO every 8 hours; Day 3: 1 mg PO every 8 hours; Day 4: 1 mg PO every 12 hours; Day 5: 1 mg PO at bedtime.
        • Symptom-triggered schedule
          • Lorazepam Oral tablet; Adults: Day 1 and 2: 2 mg PO every 6 hours PRN; Day 3: 1 mg PO every 8 hours PRN; Day 4 and 5: 1 mg PO every 12 hours PRN.
    • Midazolam c133
      • Has the most rapid onset of action (1-2 minutes) but short duration of action
      • Can be administered intravenously, intramuscularly, or orally
        • Midazolam Hydrochloride Solution for injection; Adults: Midazolam may be considered as an alternative to commonly used benzodiazepines (e.g., lorazepam). Doses of 1 to 5 mg IV every 1 to 2 hours for mild to moderate alcohol withdrawal symptoms and 1 to 20 mg every 1 to 2 hours by continuous IV infusion for delirium tremens have been suggested from retrospective data. Case reports of larger doses exist in the literature; in 1 report delirium tremens was successfully treated with a total of 2,850 mg of midazolam administered over a 5-day period, with a rate of infusion ranging from 20 to 55 mg/hour. Until more data become available, the lowest effective dose should be used in conjunction with close monitoring for potential adverse effects on respiratory and cardiovascular function. It is advisable to periodically assess the patient for signs of fluid overload.
    • Oxazepam c134
      • Preferred in patients with liver dysfunction owing to lack of active metabolites
        • Oxazepam Oral capsule; Adults: 15—30 mg PO 3—4 times daily; geriatric patients may need a reduced initial dose.
    • Chlordiazepoxide c135
      • Longer onset and duration of action
        • Inpatient dosing
          • Chlordiazepoxide Hydrochloride Oral capsule; Adults: The suggested initial dose is 50 to 100 mg PO, may repeat q4h to q6h PRN until agitation is controlled. Then reduce to lowest maintenance dose. Max: 300 mg/day PO. Hold doses if overly sedated or lethargic.
      • Example of outpatient oral chlordiazepoxide dosing regimens r10
        • Fixed-schedule
          • Chlordiazepoxide Hydrochloride Oral capsule; Adults: Day 1: 25 to 50 mg PO every 6 hours; Day 2: 25 to 50 mg PO every 8 hours; Day 3: 25 to 50 mg PO every 12 hours; Day 4 and 5: 25 to 50 mg PO at bedtime.
        • Symptom-triggered schedule
          • Chlordiazepoxide Hydrochloride Oral capsule; Adults: Day 1: 25 to 50 mg PO every 4 hours PRN; Day 2 and 3: 25 to 50 mg PO every 6 hours PRN; Day 4 and 5: 25 to 50 mg PO every 12 hours PRN.
    • Benzodiazepines for alcohol withdrawal syndrome.From Long D et al: The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 35(7):1005-11, 2017, Table 4.
      DrugTime to onsetActive metabolitesHalf-life in hoursTypical initial dose
      Diazepam1 to 5 minutes intravenousYes43 ± 1310 to 20 mg intravenous or oral
      Lorazepam5 to 20 minutes intravenousNo14 ± 52 to 4 mg intravenous or oral
      Midazolam2 to 5 minutes intravenous/intramuscularYes2 ± 12 to 4 mg intravenous or intramuscular
      Oxazepam2 to 3 hours oralNo8 ± 215 to 30 mg oral every 8 hours
      Chlordiazepoxide2 to 3 hours oralYes10 ± 350 to 100 mg oral
  • Barbiturates r47r57
    • Phenobarbital r58c136
      • Effective when used in combination with benzodiazepines for resistant withdrawal and delirium tremens r2
      • Paucity of data exists for use as monotherapy; therefore, monotherapy should only be considered in a patient whose condition is refractory to benzodiazepines r9
      • Patients requiring phenobarbital may require intubation and mechanical ventilation
      • Bolus dosing
        • Phenobarbital Sodium Solution for injection; Adults: 65 to 260 mg IV bolus every 15 to 30 minutes until control of symptoms is usually adequate. r2
      • Infusion
        • Phenobarbital Sodium Solution for injection; Adults: 10 mg/kg IV infusion over 30 minutes. r2
          • NOTE: Not readily titratable due to delayed peak onset of action
  • Propofol r59r60c137c138
    • Reserved for severe withdrawal refractory to benzodiazepine therapy in patients requiring intubation and mechanical ventilation r9
    • Propofol Emulsion for injection; Adults: Dosages from 5 to 100 mcg/kg/minute (0.3 to 6 mg/kg/hour) IV have been used to reduced alcohol withdrawal symptoms. Development of hypotension may occur. Evaluate clinical effects and CNS function daily to determine minimum effective dosage. r61
  • α₂ receptor agonists
    • May reduce autonomic signs and symptoms of alcohol withdrawal as an adjunct therapy without an increase in benzodiazepine cumulative doses r62r63r64
    • Clonidine r10c139
      • May be beneficial adjunct in mild withdrawal states to diminish symptoms in outpatient setting
      • Clonidine Hydrochloride Oral tablet; Adults: In one study, clonidine was dosed initially as 0.2 mg PO at 9PM on day 1; at 9AM, 1PM, and 6PM on day 2; at 9AM and 6PM on day 3; and a final dose at 9AM on day 4.
    • Dexmedetomidine r65c140
      • Clinical effects include sedation, anxiolysis, analgesia, and sympatholysis; incidence of respiratory depression is lower compared with other adjunct agents available for severe, refractory withdrawal r9
      • Adjunct treatment may lower benzodiazepine requirements and decrease need for mechanical ventilation in patients with severe, refractory withdrawal r9
      • Does not prevent or treat withdrawal seizures and may increase rate of delirium, although available data are conflicting r9
      • Dexmedetomidine Hydrochloride Solution for injection; Adults: Adjunctive therapy: Initiate infusion at 0.2 mcg/kg/hour IV; titrate by 0.2 mcg/kg/hour every 15 minutes to maintain desired clinical effect (Max dose: 1.4 mcg/kg/hour). r2
  • β-blockers
    • Atenolol c141
      • May be a beneficial adjunct in mild withdrawal states to diminish symptoms in outpatient setting
        • Atenolol Oral tablet; Adults: 50 to 100 mg PO once daily has been studied.
          • Pulse 50 to 79 beats per minute: 50 mg typical dose r10
          • Pulse 80 beats per minute or higher: 100 mg typical dose r10
  • Ketamine c142
    • Very limited data demonstrate safety when used as an adjunctive therapy for benzodiazepine resistant withdrawal r9r66
      • Ketamine Hydrochloride Solution for injection; Adults: Initially, a loading dose of 0.3 mg/kg, followed by 0.2 mg/kg/hour continuous IV infusion. r56r67
  • Anticonvulsants
    • May be a beneficial adjunct in mild withdrawal states to diminish craving in outpatient setting r68
    • Carbamazepine c143
      • Carbamazepine Oral capsule, Extended-Release; Adults: 300 mg PO twice daily on Days 1 through 3, 300 mg PO daily on Day 4, and 100 mg PO daily on Day 5. Individualize dosage based on clinical response and tolerability. r69r70
    • Valproic acid c144
      • Valproic Acid Oral capsule; Adults: 600 mg PO twice daily for Days 1 and 2, 300 mg PO daily on Days 3 and 4. Individualize dosage based on clinical response and tolerability. r10r71
    • Gabapentin r10c145
      • Misuse has been reported and caution should be taken especially in patients with substance use disorder r72r73
      • Gabapentin Oral capsule; Adults: Use not FDA-approved, but has been studied. Initially, 300 mg PO at bedtime on day 1; then 300 mg PO twice daily on day 2; then 300 mg PO 3 times per day on Day 3; and then titrated upward over days 4 to 7 to reach final dosage. Doses from 600 mg/day to 1,800 mg/day PO have improved abstinence rates and relapse-related symptoms (i.e., insomnia, dysphoria, craving) in some patients.
  • Thiamine (vitamin B₁) r15
    • Prophylactic dose c146
      • Vitamin B₁ (Thiamine Hydrochloride) Oral tablet; Adults: 100 mg PO once daily for 3 to 5 days. r42
      • Vitamin B₁ (Thiamine Hydrochloride) Solution for injection; Adults: 100 mg IV once daily for 3 to 5 days. r2r9
    • Treatment dose for Wernicke encephalopathy c147
      • Thiamine should be given before any glucose administration to avoid precipitating Wernicke encephalopathy;r9several dosing regimens are available r74
      • Vitamin B₁ (Thiamine Hydrochloride) Solution for injection; Adults: 500 mg IV every 8 hours for 5 days, followed by 250 mg IV once daily for 3 to 5 days depending on response. r2r11r22r75
  • Folate supplementation c148
    • Folic Acid Oral tablet; Adults: 1 mg PO once daily for 3 to 5 days. r2
    • Folic Acid Solution for injection; Adults: 1 mg IV once daily for 3 to 5 days. r2
  • Doses and pharmacologic properties of common sedative hypnotics used in the treatment of alcohol withdrawal.*All doses on the table are for the IV form of the drug except for chlordiazepoxide because the IV form of this drug has been discontinued in the United States. †Based on longer half-life of lorazepam (and diazepam), infusion dosing generally not recommended. §Case reports of infusion rates up to 520 mg/hour. (Wolf KM et al: Prolonged delirium tremens requiring massive dosages of medication. J Am Board Fam Pract. 6(5):502-4, 1993) **Generally, not given in true infusions.Adapted from Stehman CR et al: A rational approach to the treatment of alcohol withdrawal in the ED. Am J Emerg Med. 31(4):734-42, 2013, Table 1.
    ChlordiazepoxideDiazepamLorazepamMidazolamPhenobarbitalPropofol
    Class of drugBenzodiazepineBenzodiazepineBenzodiazepineBenzodiazepineBarbiturateHypnotic
    Intermittent initial dose50 to 100 mg (oral)*10 mg (intravenous)2 mg (intravenous)1 to 5 mg (intravenous)65 mg (intravenous)Not applicabler61
    Route of doseOralIntravenous, intramuscular, oral, rectalIntravenous, intramuscular, oralIntravenous, intramuscular, oralIntravenous, intramuscular, oral, rectalIntravenous
    Infusion dosingNot applicableNot applicable1 to 4 mg/hour†r561 to 20 mg/hour, titrate up to effect§10 mg/kg intravenous over 30 minutes**r20.3 to 6 mg/kg/hour as needed for appropriate sedationr61
    Time to effect onset2 to 3 hours1 to 5 minutes (intravenous); 15 to 30 minutes (intramuscular); 30 to 90 minutes (oral); 10 to 45 minutes (rectal)5 to 20 minutes2 to 5 minutes5 to 30 minutes (peak brain concentrations at 20 to 40 minutes)1 to 2 minutes
    Half life5 to 30 hours (active metabolite 30 to 200 hours)30 to 60 hours (active metabolite 30 to 100 hours)9 to 21 hours2 to 6 hours50 to 140 hours10 minutes to 12 hours (longer if prolonged use)
    Duration of actionLongLongShort to mediumShortLongShort to medium
    MetabolismHepaticHepaticHepaticHepatic, gutHepaticHepatic
    ExcretionRenalRenalRenal, fecalRenalRenalRenal
    Dose adjustmentRenal (creatinine clearance less than 10): 50% dose reduction; hepatic impairment: risk of accumulationHepatic impairment; renal impairmentRenal impairment: dose reductionRenal failure (creatinine clearance less than 10): dose reductionRenal failure (GFR less than 10): increase dosing interval and dose reduction; caution in hepatic impairmentNone
    NotesExtremely long-acting active metabolite, so not recommended in elderly patientsPhlebitis; erratic absorption if given intramuscularlyIf more than 25 mg/hour, risk of acute tubular necrosis, lactic acidosis, and hyperosmolar state because of solvent; no active metaboliteProlonged sedation if obese and/or low albumin; active metaboliteMay cause hypotensionRisks: propofol infusion syndrome, injection site pain, hypertriglyceridemia; more hypotension than other sedative-hypnotics; may discolor urine. Caution: soy or egg allergy

Nondrug and supportive care

Electrolytes c149c150

  • Electrolyte abnormalities are common in patients with long-term alcohol use and those with severe withdrawal; correct in standard manner when indicated r24
    • Hypokalemia is not uncommon; usually results from dietary deficiency
      • Potassium may require repletion depending on severity of deficiency and presence of symptoms related to deficiency r2
    • Hypomagnesemia and hypophosphatemia may occur; usually result from dietary deficiency
      • Routine supplementation is not recommended r9
      • Supplementation may be required, especially when symptomatic, given supporting laboratory evidence of severe deficiency
      • Self-correction with proper nutrition is preferred treatment for asymptomatic, mild to moderate deficiency
      • IV repletion is not routinely required r2

Fluids c151c152

  • IV fluid resuscitation may be necessary in patients with severe withdrawal
  • Increased fluid losses are not uncommon in patients with hyperthermia, hyperventilation, diaphoresis, and/or agitation r6

Nutrition r4

  • Thiamine d7
    • Thiamine is a critical cofactor in carbohydrate metabolism; deficiency results in decreased glucose utilization r2
    • Thiamine deficiency is often present and increases risk of Wernicke encephalopathy (eg, altered mental status, ophthalmoplegia, ataxia) r2
    • Administer prophylactic dose for presumed thiamine deficiency to all patients presenting in withdrawal r2r15
    • Administer treatment dose to any patients with concerning manifestations for Wernicke encephalopathy r2
    • Administer thiamine before (preferred) or with glucose administration r9
  • Folate
    • Supplementation is recommended owing to low dietary folate intake, which may lead to megaloblastic anemia in patients with long-term alcohol use disorder r2
    • Multivitamins containing daily recommended allowance of folic acid are often used r9
  • Provide nutritional support to those with long-term alcohol use to prevent and/or treat ketoacidosis
    • Route of administration is individualized r4
      • Enteral is preferred (oral, nasogastric, or nasoduodenal) c153c154
      • Parenteral may be required c155
  • Glucose c156
    • Some patients may require glucose supplementation for hypoglycemia because of increased metabolic requirements in the setting of diminished glycogen stores r6
    • Untreated hypoglycemia can lead to alcoholic ketoacidosis (hyperketonemia with anion gap metabolic acidosis without significant hyperglycemia), complicating withdrawal management
    • Avoid glucose administration alone (without thiamine administration) in patient at risk for Wernicke encephalopathy
Procedures
c157

Comorbidities

  • Liver failure c158
    • IV lorazepam and oral oxazepam may be preferred in patients with advanced cirrhosis, hepatitis, and liver failure owing to the lower degree of hepatic metabolism compared with other benzodiazepines r2r6
    • Duration of any benzodiazepines may be significantly prolonged in patients with hepatic dysfunction; dose adjustment may be required r2
  • Renal insufficiency c159
    • Most benzodiazepines and their metabolites are eliminated by the kidney; dose adjustment may be necessary, particularly in agents with active metabolites r24
  • Wernicke encephalopathy c160
    • Administer treatment dose of thiamine for duration of 3 to 5 days to any patients with concerning manifestations for Wernicke encephalopathy r2r11
    • Administer thiamine before (preferred) or with glucose administration to avoid precipitating Wernicke encephalopathy in patients at risk r9r11

Special populations

  • Pregnant women
    • There are no structured guidelines or high-level studies regarding optimal treatment of alcohol withdrawal in pregnancy r76
    • As maternal health is vitally important to fetal health, benzodiazepines should still be considered first line treatment
    • Manage in consultation with specialist (eg, substance misuse medicine, high-risk obstetrician)

Monitoring

  • Admitted patients with alcohol withdrawal syndrome and patients at risk for developing alcohol withdrawal syndrome
    • Serial measurements using a validated withdrawal severity scale are required to guide symptom-triggered treatment r4c161c162c163c164c165c166
      • Frequency of scoring depends on stage of management and degree of symptom control
        • Frequent evaluations (eg, every 10-15 minutes) may be required during initial stages of treatment r2
        • Scoring evaluations may be spaced to hourly once treatment goals are reached r2
    • Maintain awareness and assess for other coexistent conditions and alternate medical causes for patient decompensation other than worsening or recalcitrant withdrawal r2
    • Monitor for adequacy of airway protection, frequent vital signs, and hydration status r9c167c168c169
  • Outpatient monitoring for patients requiring treatment
    • Guide monitoring type and frequency based on symptom severity and characteristics of individual patient and environment r10
    • Daily reassessments are required in most patients until symptoms abate, including: r10
      • Measurement of vital signs c170
      • Random alcohol breath analysis c171
      • Withdrawal symptom severity scale assessment (eg, Short Alcohol Withdrawal Score, Clinical Institute Withdrawal Assessment for Alcohol [Revised]) c172
    • Refer for long-term outpatient treatment when symptoms are minimal, benzodiazepines are no longer required, and patient has abstained from alcohol intake for at least 3 days r10c173
    • Refer to addiction medicine specialist or inpatient treatment program if patient does not adequately respond to benzodiazepine therapy, misses an appointment, or resumes drinking alcohol r10c174c175c176
  • Refer to regional protocols to guide monitoring strategy r22

Complications and Prognosis

Complications

  • Death
    • Cause of death usually results from hyperthermia, cardiac arrhythmias, complications of withdrawal seizures, or concomitant medical disorders (eg, pneumonia, acute coronary syndromer7) r11c177c178c179c180c181
  • Aspiration pneumonia and/or respiratory depression requiring tracheal intubation and mechanical ventilation d8
  • Rhabdomyolysis d9
    • May result from severe agitation, hyperthermia, prolonged seizures, and/or prolonged use of physical restraints c184c185c186c187
  • Wernicke encephalopathy c188d7
    • Alcohol use disorder may result in chronic thiamine deficiency characterized by cell damage to the mammillary body, thalamus, and hippocampus r15
      • May lead to the permanent amnestic syndrome or Korsakoff encephalopathy
    • Prevalence may be as high as 3% r7
    • Classically presents with confusion, ataxia, and ophthalmoplegia r15
    • Glucose administration without thiamine replacement can precipitate syndrome in thiamine-deficient patients r15
    • Diagnosis may be missed if nystagmus and ataxia are not appreciated; mental status changes may be attributed to delirium tremens r7

Prognosis

  • Overall prognosis is best among patients without other acute medical problems r4
  • Morbidity and mortality are increased among patients with comorbidity, concurrent disease related to alcohol use disorder that complicates management,r4 and older ager5
    • Failure to identify an underlying medical or surgical issue leading to decreased alcohol intake places patient at increased risk for morbidity and mortality
  • Mortality among hospitalized patients with delirium tremens is about 1% to 4% r2
  • Long-term mortality among patients who experience seizures or delirium tremens associated with withdrawal episode is guarded
    • Up to 50% of patients die within 10 years r9
  • Clinical course
    • Symptoms of acute withdrawal usually improve markedly by several days after abstinence r3
    • Persistent symptoms (eg, anxiety, insomnia, autonomic dysfunction) may occur in some patients for up to 6 months r3
      • Symptoms occur at lower level of intensity than during acute withdrawal
    • About 5% of patients who develop acute withdrawal will progress to severe withdrawal without treatment r77
    • About one-third of patients who develop seizures will progress to delirium tremens without treatment r2
    • Average length of hospitalization for acute withdrawal
      • General inpatients: about 5.4 days r4
      • ICU patients: about 12.5 days r4
    • Patients who develop delirium
      • Delirium usually subsides within a few days; rarely persists for up to 2 weeks r4
      • Return to baseline mental status may require several weeks for some patients r4
    • Long-term abstinence from alcohol among patients with alcohol use disorder r10
      • First step is successful treatment of withdrawal
      • Enrollment in a long-term treatment program greatly increases likelihood of long-term abstinence
  • Recurrent withdrawal
    • Subsequent episodes of alcohol withdrawal tend to increase in severity r78

Screening and Prevention

Screening

At-risk populations

  • Hospitalized and patients with active alcohol use disorder may be at increased risk d10

Screening tests

  • Prediction of Alcohol Withdrawal Severity Scale may predict complicated withdrawal among hospitalized patients r8c189
    • Score of 4 or higher suggests high risk for developing moderate to severe withdrawal r17
      • Sensitivity is approximately 93% and specificity is approximately 99% r8
    • Scoring questions are as follows: r79
      • Have you consumed any amount of alcohol within the last 30 days? Or did the patient have a positive blood alcohol content on admission?
        • If no, then stop. Prediction of Alcohol Withdrawal Severity Scale is negative
        • If yes, then continue to score 1 point for each of the following:
          • Have you been recently intoxicated/drunk, within the last 30 days?
          • Have you ever undergone alcohol use disorder rehabilitation treatment or treatment for alcoholism?
          • Have you ever experienced any previous episodes of alcohol withdrawal, regardless of severity?
          • Have you ever experienced blackouts?
          • Have you ever experienced alcohol withdrawal seizures?
          • Have you ever experienced delirium tremens or DTs?
          • Have you combined alcohol with other "downers" like benzodiazepines or barbiturates, during the last 90 days?
          • Have you combined alcohol with any other substances of abuse, during the last 90 days?
          • Was the patient’s blood alcohol content on presentation 200 mg/dL or higher?
          • Is there evidence of increased autonomic activity (eg, heat rate above 120 beats per minute, tremor, sweating, agitation, nausea)?

Prevention

  • Ask all patients about their alcohol use r6r80
    • Counsel patients with frequent alcohol use to limit consumption to a safe level c190c191
    • Consider referral to an alcohol or substance use specialist if patient cannot self-limit alcohol intake c192
  • Enrollment in long-term treatment program after an episode of withdrawal decreases likelihood of relapse and future episodes of withdrawal r10c193
McMicken D et al: Alcohol-related seizures. Emerg Med Clin North Am. 29(1):117-24, 201121109108Long D et al: The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 35(7):1005-11, 201728188055American Psychiatric Association: Alcohol withdrawal. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013:499-501Carlson RW et al: Alcohol withdrawal syndrome. Crit Care Clin. 28(4):549-85, 201222998991Kosten TR et al: Management of drug and alcohol withdrawal. N Engl J Med. 348(18):1786-95, 200312724485Stehman CR et al: A rational approach to the treatment of alcohol withdrawal in the ED. Am J Emerg Med. 31(4):734-42, 201323399338Finn K: Inpatient management of alcohol withdrawal. Hosp Med Clin. 1(1):e132-47, 2012http://www.sciencedirect.com/science/article/pii/S2211594311000098Maldonado JR et al: Prospective validation study of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) in medically ill inpatients: a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol Alcohol. 50(5):509-18, 201525999438Schmidt KJ et al: Treatment of severe alcohol withdrawal. Ann Pharmacother. 50(5):389-401, 201626861990Muncie HL Jr et al: Outpatient management of alcohol withdrawal syndrome. Am Fam Physician. 88(9):589-95, 201324364635Schuckit MA: Recognition and management of withdrawal delirium (delirium tremens). N Engl J Med. 371(22):2109-13, 201425427113Hall W et al: The alcohol withdrawal syndrome. Lancet. 349(9069):1897-900, 19979217770National Institute on Alcohol Abuse and Alcoholism: Drinking Levels Defined. NIAAA website. Accessed September 14, 2018. https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinkinghttps://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinkingGoodson CM et al: Predictors of severe alcohol withdrawal syndrome: a systematic review and meta-analysis. Alcohol Clin Exp Res. 38(10):2664-77, 201425346507Sachdeva A et al: Alcohol withdrawal syndrome: benzodiazepines and beyond. J Clin Diagn Res. 9(9):VE01-7, 201526500991Alcohol, Ethanol. In: ToxED [database online]. Tampa, FL: Elsevier; 2018. Updated August 1, 2018. Accessed September 14, 2018. http://www.toxed-ip.com/ToxEdView.aspx?id=592345http://www.toxed-ip.com/ToxEdView.aspx?id=592345Simpson SA et al: Psychiatric emergencies for clinicians: emergency department management of alcohol withdrawal. J Emerg Med. 51(3):269-73, 201627319379Friedmann PD: Alcohol use in adults. N Engl J Med. 368(17):1655-6, 201323614598Eyer F et al: Risk assessment of moderate to severe alcohol withdrawal--predictors for seizures and delirium tremens in the course of withdrawal. Alcohol Alcohol. 46(4):427-33, 201121593124Sullivan JT et al: Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar). Br J Addict. 84(11):1353-7, 19892597811Sessler CN et al: The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 166(10):1338-44, 200212421743National Institute for Health and Care Excellence: Alcohol-use Disorders: Diagnosis and Management of Physical Complications. Clinical Guideline CG100. NICE website. Published June 2010. Updated April 2017. Accessed September 14, 2018. https://www.nice.org.uk/guidance/cg100https://www.nice.org.uk/guidance/cg100Awissi DK et al: Alcohol withdrawal and delirium tremens in the critically ill: a systematic review and commentary. Intensive Care Med. 39(1):16-30, 201323184039Allison MG et al: Alcoholic metabolic emergencies. Emerg Med Clin North Am. 32(2):293-301, 201424766933Bird RD et al: Alcohol withdrawal: what is the benzodiazepine of choice? Ann Pharmacother. 28(1):67-71, 19948123967American Psychiatric Association: Delirium, diagnostic criteria. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013:596-601Wartenberg AA: Management of alcohol intoxication and withdrawal. In: Ries RK et al, eds: The ASAM Principles of Addiction Medicine. 5th ed. Philadelphia, PA: Wolters Kluwer Health; 2014:635-51Galameau DW et al: Benzodiazepine intoxication and withdrawal: assessment and management. Hosp Med Clin. 4(4):513-25, 2015http://www.sciencedirect.com/science/article/pii/S2211594315000313McKeon A et al: The alcohol withdrawal syndrome. J Neurol Neurosurg Psychiatry. 79(8):854-62, 200817986499Ross JC et al: Acute intrathecal baclofen withdrawal: a brief review of treatment options. Neurocrit Care. 14(1):103-8, 201120717751McMicken DB: Alcohol withdrawal syndromes. Emerg Med Clin North Am. 8(4):805-19, 19902226288Ciccarone D: Stimulant abuse: pharmacology, cocaine, methamphetamine, treatment, attempts at pharmacotherapy. Prim Care. 38(1):41-58, v-vi, 201121356420Schneider P et al: A case of mistaken identity: alcohol withdrawal, schizophrenia, or central pontine myelinolysis? Neuropsychiatr Dis Treat. 8:49-54, 201222347796American Psychiatric Association: Schizophrenia. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013:99-105Davies H et al: Listeria meningoencephalitis masked by alcohol withdrawal. J R Soc Med. 92(4):196-7, 199910450200Devereaux D et al: Hyperthyroidism and thyrotoxicosis. Emerg Med Clin North Am. 32(2):277-92, 201424766932Amato L et al: Efficacy and safety of pharmacological interventions for the treatment of the alcohol withdrawal syndrome. Cochrane Database Syst Rev. CD008537, 201121678378Jawa RS et al: Alcohol withdrawal syndrome in admitted trauma patients. Am J Surg. 208(5):781-7, 201425062967Jung ME et al: Alcohol withdrawal and brain injuries: beyond classical mechanisms. Molecules. 15(7):4984-5011, 201020657404Marra A et al: Intensive care unit delirium and intensive care unit-related posttraumatic stress disorder. Surg Clin North Am. 97(6):1215-35, 201729132506Setters B et al: Delirium. Prim Care. 44(3):541-59, 201728797379Stephens JR et al: Who needs inpatient detox? Development and implementation of a hospitalist protocol for the evaluation of patients for alcohol detoxification. J Gen Intern Med. 29(4):587-93, 201424395104Guglielmo R et al: Pharmacological treatments in alcohol use disorders: state of art and new perspectives. Clin Ter. 166(6):262-70, 201526794815Daeppen JB et al: Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. 162(10):1117-21, 200212020181New York-Presbyterian Hospital: Alcohol Withdrawal (AWD) Symptom-triggered Therapy Guidelines (Pilot) for Medical Patients (NYP/CU: Emergency Department, Medical ICU/A and B, 6GN/S, and 7GS). Columbia University Medical Center website. Issued June 2009. Reviewed May 2010. Approved May 2012. Accessed September 14, 2018. http://www.hospitalist.cumc.columbia.edu/downloads/clinical%20references/Alcohol_Withdrawal_-Guideline_Adult_.pdfhttp://www.hospitalist.cumc.columbia.edu/downloads/clinical%20references/Alcohol_Withdrawal_-Guideline_Adult_.pdfMonte-Secades R et al: Inpatient alcohol withdrawal syndrome. Rev Clin Esp. 215(2):107-16, 201525559647Rosenson J et al: Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 44(3):592-8.e2, 201322999778Mayo-Smith MF: Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 278(2):144-51, 19979214531Minozzi S et al: Anticonvulsants for alcohol withdrawal. Cochrane Database Syst Rev. CD005064, 201020238337Mee-Lee D: Understanding and Utilizing ASAM Placement Criteria. National Association for Alcoholism and Drug Abuse Counselors website. Published March 14, 2012. Accessed September 14, 2018. https://www.naadac.org/assets/1959/2012-03-14_understanding_and_utilizing_asam_webinarslides.pdfhttps://www.naadac.org/assets/1959/2012-03-14_understanding_and_utilizing_asam_webinarslides.pdfAlcoholics Anonymous website. Accessed September 14, 2018. https://www.aa.org/https://www.aa.org/National Council on Alcoholism and Drug Dependence (NCADD) website. Accessed September 14, 2018. https://www.ncadd.org/https://www.ncadd.org/National Institute on Alcohol Abuse and Alcoholism (NIAAA) website. Accessed September 14, 2018. https://www.niaaa.nih.gov/https://www.niaaa.nih.gov/Substance Abuse and Mental Health Services Administration: National Recovery Month. SAMHSA website. Accessed September 14, 2018. https://www.recoverymonth.gov/https://www.recoverymonth.gov/Substance Abuse and Mental Health Services Administration (SAMHSA) website. Accessed September 14, 2018. https://www.samhsa.gov/https://www.samhsa.gov/Shah P et al: Adjunctive use of ketamine for benzodiazepine-resistant severe alcohol withdrawal: a retrospective evaluation. J Med Toxicol. 14(3):229-36, 201829748926Mo Y et al: Barbiturates for the treatment of alcohol withdrawal syndrome: a systematic review of clinical trials. J Crit Care. 32:101-7, 201626795441Hendey GW et al: A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. Am J Emerg Med. 29(4):382-5, 201120825805Erstad BL et al: Management of alcohol withdrawal. Am J Health Syst Pharm. 52(7):697-709, 19957627738Hughes JR: Alcohol withdrawal seizures. Epilepsy Behav. 15(2):92-7, 200919249388Brotherton AL et al: Propofol for treatment of refractory alcohol withdrawal syndrome: a review of the literature. Pharmacotherapy. 36(4):433-42, 201626893017Muzyk AJ et al: Dexmedetomidine for the treatment of alcohol withdrawal syndrome: rationale and current status of research. CNS Drugs. 27(11):913-20, 201323975661Muzyk AJ et al: Role of α2-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother. 45(5):649-57, 201121521867Linn DD et al: Dexmedetomidine for alcohol withdrawal syndrome. Ann Pharmacother. 49(12):1336-42, 201526400008Mueller SW et al: A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med. 42(5):1131-9, 201424351375Wong A et al: Evaluation of adjunctive ketamine to benzodiazepines for management of alcohol withdrawal syndrome. Ann Pharmacother. 49(1):14-9, 201525325907Pizon AF et al: Adjunct ketamine use in the management of severe ethanol withdrawal. Crit Care Med. 46(8):e768-71, 201829742583Barrons R et al: The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. J Clin Pharm Ther. 35(2):153-67, 201020456734Malcolm R et al: The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen Intern Med. 17(5):349-55, 200212047731Schik G et al: Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal. Addict Biol. 10(3):283-8, 200516109591Lum E et al: Valproic acid management of acute alcohol withdrawal. Ann Pharmacother. 40(3):441-8, 200616507623Drug Enforcement Administration, Office of Diversion Control, Drug & Chemical Evaluation Section: Gabapentin (Neurontin). US Department of Justice website. Published March 2018. Accessed September 14, 2018. https://www.deadiversion.usdoj.gov/drug_chem_info/gabapentin.pdfhttps://www.deadiversion.usdoj.gov/drug_chem_info/gabapentin.pdfSmith RV et al: Gabapentin misuse, abuse and diversion: a systematic review. Addiction. 111(7):1160-74, 201627265421Latt N et al: Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders. Intern Med J. 44(9):911-5, 201425201422Lingford-Hughes AR et al: BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP. J Psychopharmacol. 26(7):899-952, 201222628390Bhat A et al: The management of alcohol withdrawal in pregnancy--case report, literature review and preliminary recommendations. Gen Hosp Psychiatry. 37(3):273.e1-3, 201525708467Trevisan LA et al: Complications of alcohol withdrawal: pathophysiological insights. Alcohol Health Res World. 22(1):61-6, 199815706735Monte R et al: Risk factors for delirium tremens in patients with alcohol withdrawal syndrome in a hospital setting. Eur J Intern Med. 20(7):690-4, 200919818288Maldonado JR et al: The "Prediction of Alcohol Withdrawal Severity Scale" (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol. 48(4):375-90, 201424657098Heilig M et al: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked? Addict Biol. 15(2):169-84, 201020148778