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Mar.11.2021

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 r1r2
  • 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 r3
  • Manifestations may worsen without treatment; progression to severe symptom manifestations including seizures and delirium tremens occurs in up to 5% of patients r4
  • Withdrawal is a clinical diagnosis and a diagnosis of exclusion; DSM-5 diagnostic criteria define the diagnosis r1
  • 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 r5
  • 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 r4
  • Refer all patients with alcohol withdrawal for alcohol use disorder treatment (eg, alcohol abstinence counseling, long-term rehabilitation) r6
  • Overall prognosis is best among patients without other acute medical problems r6
  • Morbidity and mortality are increased among patients with comorbidity, concurrent disease related to alcohol use disorder that complicates management,r6 and older ager7
  • 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 r7
    • 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 r4
    • 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 r4
    • 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 r1r2
  • Severe symptom manifestations (eg, seizures, delirium tremens) may develop in up to 5% of patients r4

Classification

  • Based on severity r8
    • Uncomplicated alcohol withdrawal
      • Majority of patients have uncomplicated minor withdrawal symptoms
      • Manifestations occur early, within the first 48 hours after last drink or decrease in consumption r9
        • 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 daysr10 if withdrawal does not progress to major alcohol withdrawal syndrome r3
      • Characterized by mild to moderate 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 alcohol craving r3
    • Complicated or severe alcohol withdrawal
      • Up to 5% of patients develop a more complicated syndrome r4r11
      • Withdrawal manifestations progress and worsen, usually after about 24 hours from the onset of initial manifestations r3
      • Characterized by severe autonomic hyperactivity (eg, tachycardia, hypertension, diaphoresis, hyperreflexia, fever); marked tremor; pronounced anxiety, insomnia, or irritability; anorexia; decreased seizure threshold; hallucinations; and delirium r3
      • Manifestations often peak around 50 hours before gradual resolution or may continue to progress to severe (complicated) withdrawal, particularly without treatment r3
      • Rigorous definition is lacking r5
      • Many experts define based on presence of any of the following:
        • Withdrawal seizures r4r5
        • Delirium tremens
        • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score greater than 20 r12
        • Major alcohol withdrawal syndrome manifestations refractory to high-dose benzodiazepines r5
  • Based on progressive stages r6
    • Stage 1
      • Minor symptoms not usually associated with significantly abnormal vital signs r12
    • Stage 2
      • Mild to moderate symptoms associated with abnormal vital signs and possibly alcoholic hallucinosis r12
    • 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 r12

Diagnosis

Clinical Presentation

Characteristic withdrawal syndrome develops within hours to days after cessation or reduction of heavy and prolonged alcohol use r1

  • Probability of developing withdrawal rises with increasing quantity and frequency of alcohol consumption r1
    • Most affected patients are drinking daily for multiple days and consuming large amounts (ie, more than 8 drinks/day for multiple days) r1r5
  • Symptoms typically begin after sharp decline in blood alcohol concentration r1
  • Reduction or cessation in alcohol use may not always be intentional r6r13
    • Inability to acquire or pay for alcohol
    • Gastrointestinal illness characterized by decreased oral intake
    • Hospital admission for another medical issue r7
      • Up to 8% of patients admitted to hospitals with non–alcohol-related diagnoses exhibit signs of withdrawal

Earlier medical history may be significant for: r6

  • 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 r9r11
    • Suspect alcohol dependence in female patients who: r12
      • 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)r14
    • Suspect alcohol dependence in male patients who: r12
      • 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)r14
  • History of prior withdrawal
    • Course of prior alcohol withdrawal episodes is the most reliable predictor of subsequent episodes r15

Psychiatric history

  • Alcohol may cause several psychiatric conditions such as alcohol-induced mood, anxiety, or psychotic disorder r6
  • 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 r1
  • Concurrent use of medication for other underlying disorders (eg, β-blockers, α₂-adrenergic agonists) may blunt typical abnormalities noted in vital signs at presentation r4

Presence of comorbidity

  • Patients with underlying psychiatric disorders may use alcohol to alleviate psychiatric symptoms such as anxiety and depression r6
  • Acute medical or surgical disorder may precipitate withdrawal r6
  • Poorly controlled medical comorbidity may precipitate withdrawal r6

Acute withdrawal may progress in stages ranging in severity from mild to severe r16

  • Manifestations during stages may overlap and may not progress in a precise sequential pattern r6
  • Early withdrawal: symptoms of central nervous system stimulation typically occurring within 48 hours of drinking cessation r9
    • Stage 1 (hangover stage)
      • Initial broad withdrawal manifestations begin 6 to 8 hours after last drink and may include: r4
        • 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 r4
    • Stage 2 (alcoholic hallucinosis stage)
      • Develops approximately 24 to 48 hours after last drink; may be up to 8 days r6
      • 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 r4
        • Occur in 7% to 8% of untreated patients with withdrawal r4
        • Can be visual, auditory, or tactile r4
        • May occur in isolation without other broad withdrawal manifestations
        • Sensorium is normal (ie, delirium is absent; patient is aware that hallucinations are not real) r9
    • Stage 3 (tonic-clonic seizure stage)
      • Similar to stage 2 with development of tonic-clonic seizures r6c20c21c22c23c24
      • Withdrawal seizures (rum fits)
        • Commonly occur 12 to 48 hours after last drink r4
        • May occur in up to 10% of patients r2
          • Alcohol withdrawal represents 1 of the most common causes of adult-onset seizures r3c25
        • Commonly consist of isolated, short-duration, generalized tonic-clonic seizures with short or absent postictal period r2c26c27c28c29
          • May occur in clustersr6r18 and may be recurrent in a minority of patients r9r6
          • Prolonged seizures and status epilepticus are relatively uncommon r6c30c31
        • Seizures impart increased risk for complications (eg, aspiration pneumonia, rhabdomyolysis) r6
        • 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 r9
    • Stage 4 (delirium tremens stage)
      • High likelihood that a concurrent, clinically relevant medical condition exists when delirium develops r1
        • 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: r5
            • Lack of attention and awareness c32c33
            • Memory loss and disorientation c34c35
            • Hallucinations c36
            • Agitation r9c37
        • 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 r4r6
          • Rarely, may develop as early as 8 hours after last drink r4
        • Often associated with cardiovascular, respiratory, and metabolic abnormalities r6
        • Occurs in 1% to 5% of hospitalized patients with withdrawal r4r6
        • Risk is significantly increased in patients with concurrent acute medical illness r6

Physical examination

  • Common findings r2r6
    • 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 r6
      • 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) r4
        • Inhibited excitatory tone occurs through NMDA receptor modulation (affecting several proteins involved in N-methyl-D-aspartate pathways) r4
      • Alcohol administration increases catecholamine levels affecting central α- and β-adrenergic receptors r3r6
      • 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 r4
    • Dopaminergic dysregulation may also play a role in agitation, hallucinations, and delirium r9
    • 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 r3r6
    • 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 r1
    • Most commonly in middle-aged adults r6c55
    • Relatively rare in patients younger than 30 years r1
  • Older patients are at increased risk for morbidity and mortality r7c56c57
Sex
  • Most patients admitted to hospitals with alcohol withdrawal syndrome are male r6c58c59
Other risk factors/associations
  • Risk factors for withdrawal
    • Risk increases linearly with quantity and frequency of alcohol intake r5c60
    • Concurrent medical condition that precludes alcohol intake r1
    • Family history of alcohol withdrawal r1c61
    • Personal history of alcohol withdrawal r1
    • Concurrent long-term use and then discontinuation of sedative, hypnotic, or anxiolytic drugs r1c62c63
    • Patients with tolerance phenomenon r9c64
  • Risk factors for severe withdrawal course are inconsistently reported in literature but may include:
    • Prior episode of withdrawal, especially severe withdrawal r18c65
    • Drinking patterns that include: r6
      • 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 r1r19c66
    • Acute and chronic comorbid medical problems (eg, alcoholic liver disease, cointoxications, trauma, infections, sepsis, history of structural brain lesionr20) r6c67c68c69c70c71c72
    • Nonmedical use of sedative hypnotics r6c73
    • Detectable blood alcohol level on admission with withdrawal manifestations r6c74
    • Severe symptoms early in withdrawal course r9
    • Grade 2 severity or higher on presentation (initial Clinical Institute Withdrawal Assessment for Alcohol [Revised] score greater than 10) r6c75
    • Abnormal liver function (serum AST activity above 80 units/L) r6c76
    • Presence of significant dehydration or electrolyte abnormalities at presentation r16c77c78
    • Low initial platelet count and/or serum potassium level r15r20c79c80
    • Male sex r6
  • Risk factors for delirium tremens are inconsistently reported in literature but may include:
    • Concurrent medical illness (eg, pneumonia, active ischemia) r9c81c82
    • History of delirium tremens r11c83
    • Withdrawal seizures, specifically if left untreated or recurrent r9r11c84
    • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score of 15 or higher r11c85
    • Sustained drinking history r4c86
    • Systolic blood pressure above 150 mm Hg and/or heart rate above 100 beats per minute r11c87c88
    • Last alcohol intake more than 2 days ago r4c89
    • Age older than 30 years r4c90
    • Recent misuse of other depressants (eg, benzodiazepines) r11c91c92

Diagnostic Procedures

Primary diagnostic tools

  • If patients present with clinical manifestations of alcohol withdrawal, assess quantity and frequency of alcohol consumption and time last consumed r21
    • Consider use of screening tool for unhealthy alcohol use
    • May gain additional information from family or friends
    • May use alcohol breath, blood, or urine test to identify recent alcohol use if patient is unable to give history
  • Withdrawal is a clinical diagnosis and a diagnosis of exclusion r4
    • 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 r16
  • Measure severity of withdrawal with applicable severity assessment tool
    • Several scales are available; most commonly used include:
      • Short Alcohol Withdrawal Scale r12
        • 10-item scale requiring patient participation; most common tool used for outpatients
      • Clinical Institute Withdrawal Assessment for Alcohol (Revised) scale r6r22
        • 10-item scale requiring patient cooperation; most common tool used for inpatients
      • Richmond Agitation-Sedation Scale r6r23
        • 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 r4r16
  • Evaluate risk for severe or complicated withdrawal using risk assessment tool r21
    • The following factors increase risk for complicated withdrawal or complications associated with withdrawal
      • History of previous alcohol withdrawal delirium or seizure
      • Numerous past episodes of withdrawal
      • Comorbid conditions
      • Age older than 65 years
      • Long duration of heavy alcohol use
      • Seizure during this presentation
      • Marked autonomic hyperactivity
      • Dependence on benzodiazepines or barbiturates
      • Moderate or worse withdrawal at presentation
    • Risk assessment tools include the ASAM (American Society of Addiction Medicine) Criteria Risk Assessment Matrix, Prediction of Alcohol Withdrawal Severity Scale, and Luebeck Alcohol Withdrawal Risk Scale r24
  • Evaluate for other disease that may have contributed to precipitation of withdrawal r4
    • Consider presence of concomitant condition or complication of long-term alcohol use, especially in the presence of severe withdrawal (eg, delirium) r1
      • Withdrawal is often precipitated in patients with comorbid medical or surgical conditions during periods of abstinence when illness or surgery prevents alcohol intake r6
      • 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 r4
  • Evaluate for other substance use r21
  • 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) r6r12
    • Obtain finger stick glucose measurement for all patients with altered mental status or seizures r18
    • Most experts order the following:
      • Metabolic panel with serum electrolyte, magnesium, phosphate, and glucose levels, plus renal function testing r18
      • CBC r18
      • Liver function tests, including INR and serum AST, ALT, bilirubin, and ammonia r18
    • Consider the following:
      • Head CT or other brain imaging for patients with seizures: only attribute seizure to alcohol withdrawal if there is recent cessation or marked reduction in alcohol consumption r16r21
      • 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
      • Screening for hepatitis, HIV, and tuberculosis r21
  • Refer to regionally specified protocols to guide evaluation strategy r25

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 r1
      • Anticipate worsening of withdrawal manifestations as ethanol concentration falls in patients presenting with alcohol withdrawal and an elevated ethanol concentration r4
  • Metabolic panel with serum electrolyte (including magnesium) and glucose levels r26c106c107c108c109
    • Abnormal findings are common in long-term alcohol use and may include: r27
      • Hypoglycemia
      • Hypokalemia
      • Hypomagnesemia
      • Hypophosphatemia
  • Renal function tests (BUN, creatinine) c110c111
    • Renal insufficiency can guide choice of doses in treatment r28
  • 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 r28

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 r1c116
      • 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 r29
      • 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 r12
      • 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) r22c118
    • Objectively measures severity of withdrawal and determines likelihood of progressing alcohol withdrawal syndrome; clinical uses may include: r6
      • 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 r6
      • 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 r12
        • 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 r4
    • Scores are altered by pain, other medical and surgical issues, and administration of sedation agents r6
    • 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: r12
        • 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,r30less than 8,r110 to 8r16
        • Moderate: 10 to 18,r308 to 15,r119 to 15r16
        • Severe: 19 or higher,r30higher than 15,r1116 or higherr16
  • Richmond Agitation-Sedation Scale r6r23c119c120c121
    • 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) r4
  • Prediction of Alcohol Withdrawal Severity Scale may predict complicated withdrawal among hospitalized patients r10r24c122
    • Score of 4 or higher suggests high risk for developing moderate to severe withdrawal r18
      • Sensitivity is approximately 93% and specificity is approximately 99% r10
    • Scoring questions are as follows: r31
      • 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)?

Differential Diagnosis

Most common

  • Sedative-hypnotic medication withdrawal r32r33c123
    • Withdrawal from chronically used sedative-hypnotic medications, including benzodiazepines, barbiturates, baclofen, or γ-hydroxybutyrate (GHB) r34r35
    • 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 r36c124d1
    • 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 r37c125d2
    • 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 patients with schizophrenia, 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 r38
  • Encephalitis r39c126d3
    • 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 r6c127d4
    • 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 r40c128d5
    • 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 r41c129d6
    • 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 r42r43c130
    • 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 r44c131
    • 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 r6
    • Diagnosis of delirium is clinical and based on DSM-5 diagnostic criteria r45

Treatment

Goals

  • Monitor withdrawal course and provide symptomatic treatment with aim to normalize vital signs, relieve anxiety, and halt progression to severe withdrawal r2
  • Manage severe withdrawal (eg, seizures, delirium) and monitor for complications (eg, respiratory depression, pneumonia, rhabdomyolysis) r2
  • Address and manage other comorbid or concurrent medical, surgical, traumatic, toxicologic, or psychiatric issues r6
  • Arrange for substance use disorder treatment and encourage long-term abstinence r2

Disposition

General criteria for outpatient management r12

  • 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 r25

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 r4r6r46
  • Patient not currently intoxicated (alcohol or other drugs) r4
  • No history of complicated alcohol withdrawal syndrome (ie, seizures, hallucinosis, delirium tremens) r4
  • No significant medical or psychiatric comorbidity or suicidal ideation r4r46
  • Patient ability to maintain regular outpatient visits and therapy r4

General criteria for outpatient detoxification

  • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score 15 or less r4
  • No symptoms or history of delirium tremens or alcohol withdrawal seizures r4r46
  • Ability to take oral medications r4
  • Presence of a family member or close contact who can stay with the patient r4
  • Lack of unstable medical condition r4
  • No psychosis or suicidality r4
  • Ability to commit to daily medical visits and adequate follow-up r4

Admission criteria

Admission criteria to medical unit or inpatient medically supervised detoxification center r6

  • Patients with more than mild alcohol withdrawal plus all of the following:
    • No underlying medical or surgical condition requiring ICU-level care r4
    • Normalization or near-normalization of vital signs within emergency department r4
    • Clear sensorium r4
    • Responsive to 10 to 20 mg diazepam and tolerating 2 to 4 hours between benzodiazepine doses r4
  • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score higher than 15 r46
  • Clinical Institute Withdrawal Assessment for Alcohol (Revised) score 8 to 15 and a history of delirium tremens or alcohol withdrawal seizures r46
  • 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 withdrawalr18)
  • Patients with concomitant major electrolyte disorder, decompensated medical illness,r46 psychiatric illness, or pregnancy r18
  • Presence of medical or psychiatric condition or suicidal ideation requiring inpatient admission r4
Criteria for ICU admission
  • Intubation or other respiratory support requirement r6
  • Severe hemodynamic abnormalities r6
    • Significant tachycardia or hypotension
  • Persistent fever higher than 39 °C r6
  • Severe, or advanced stage 2 or greater, withdrawalr6
    • Delirium
    • Recurrent seizures
    • Requirement for large or escalating doses of benzodiazepines or barbiturates r2r4
    • Moderate to severe withdrawal despite elevated blood alcohol concentration r4
  • Consider for patients with:
    • Significant medical or surgical comorbidities (eg, cardiac disease, respiratory disease, renal insufficiency, acute serious infection, trauma) r4r6
    • Evidence of significant alcohol-related complications (eg, hepatic insufficiency, pancreatitis, gastrointestinal bleeding, rhabdomyolysis) r4
    • History of complicated alcohol withdrawal or severe withdrawal course r4
    • Marked fluid or electrolyte abnormalities r6
    • Patients requiring treatment of suspected Wernicke encephalopathy r4
    • Older age r18

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) r9r11
  • 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 r4r8

  • Manage airway and administer oxygen as indicated clinically r18
  • Initiate fluid resuscitation and start IV fluids when clinically indicated r18
  • Treat concurrent medical conditions r18
  • Treat hypoglycemia; begin thiamine administration before glucose (preferred) r5

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 r6r11
    • May be managed with supportive care alone, carbamazepine, or gabapentin r21
    • Some experts consider prescribing brief lorazepam regimen (2-4 mg every 4 hours) as needed for 3 to 5 days r46
  • Patients with mild to moderate manifestations without significant comorbidity or significant risk of developing severe withdrawal may be managed in either: r6r12r19
    • Outpatient setting with oral medications and daily follow-up when environment is conducive for recovery
    • Benzodiazepines are the first line treatment; carbamazepine or gabapentin can be alternatives or adjunctive agents r47
    • 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: r12
    • Moderate to severe manifestations r6
    • Significant comorbid psychiatric, medical, or surgical conditions r6
    • Patients at risk for severe withdrawal r19

Regional protocols are available to guide management strategy for both inpatient and outpatient treatment r25

Standard inpatient alcohol withdrawal treatment with medical assistance r2

  • Sedative hypnotics are the cornerstone of initial management r5
    • Goal of initial treatment is rapid sedation with normalization of vital signs r2
      • Consider alternative or concurrent diagnosis if appropriate sedation is achieved without normalization of vital signs r18
      • Appropriately sedated patient is calm and sleepy but arousable without active hallucinations or seizures r23
      • 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 r41r48
      • 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 r4
      • Preferred methods of administration include:
        • IV route for severe symptoms; oral route for less severe symptoms r4
        • Front-loading (loading dose) of benzodiazepines r49
          • 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 r4
          • Titrate based on sequential sedation scale scores r6
          • No maximum dose of benzodiazepines exists for treatment of alcohol withdrawal r4
          • Dose required to control manifestations is highly variable among patients r11
      • Debate exists regarding which benzodiazepine is the best treatment option r4
        • Some clinicians prefer IV diazepam or lorazepam for acute severe symptom control r4
          • Diazepam has shorter onset of action when compared with lorazepam, which may allow more rapid determination of dose response and more frequent dose titration r5
          • Longer duration of diazepam compared with lorazepam may allow for smoother downward titration r5
          • Diazepam may require dose adjustment in patients with renal failure because active metabolites are eliminated by kidneys; avoid in patients with liver disease r5
          • 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 r9
        • Exercise caution with routine use of more than 1 type of benzodiazepine in combination; experts recommend use of only a single benzodiazepine r9
          • Use of 2 different benzodiazepines may be required in select scenarios including: r50
            • 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 r16
    • Second line adjunct treatments for withdrawal resistant to benzodiazepines alone include phenobarbital and/or propofol r4r21
      • Can work synergistically with benzodiazepines on the GABA-A receptor r2r51
        • 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 r52
      • Respiratory and cardiac depressant effects are more common than with benzodiazepines alone
      • Emerging adjunct treatments include dexmedetomidine and ketamine r4
      • Carbamazepine, phenobarbital, or gabapentin may be used when benzodiazepines are contraindicated r21
  • 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 r21r49r53
        • Symptom-triggered dosing based on severity scales allows for individualized dosing and results in shorter duration of therapy and lower cumulative medication doses r4r5
        • 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 r9r18
      • 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)
      • Front-loading is recommended for patients having severe withdrawal r21
      • Example of dosing regimen are described in the ASAM guideline on alcohol withdrawal management r21
    • Use objective measurement of symptom severity to determine frequency of administration targeted to treatment goals r4
      • 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 r4
          • Goal of treatment is a calm awake state r16
          • Suggested treatment response to score r9
            • 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 r5
        • ICU sedation scales are often used for patients with severe withdrawal or withdrawal requiring intubation r4
          • Richmond Agitation-Sedation Score is most commonly used r6
            • Score of 0 to −2 indicates patient is in a calm, arousable state r4
    • Tapering
      • Usually benzodiazepines can be tapered down from peak dosing after about 48 to 72 hours r9
      • General guideline is to taper by about 20% of total daily benzodiazepine equivalent dose r50
      • Some experts prefer chlordiazepoxide for scheduled tapering protocol; other experts prefer lorazepam given by a symptom-triggered tapering strategy r50
  • Manifestation-specific treatment
    • Seizures
      • Benzodiazepines are first line treatment r4
      • 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 r4
      • Long-term anticonvulsant therapy is not necessary unless patient has underlying seizure disorder or epilepsy r6
      • Refractory status epilepticus may require management in consultation with specialists (eg, medical toxicologist, neurologist) and infusion of phenobarbital, pentobarbital, propofol, or midazolam r3
    • Alcoholic hallucinosis
      • Benzodiazepines are first line treatment r4
      • 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,r18 and increase risk of respiratory complications r4r6
        • May be beneficial for patients with known or suspected thought disorders (eg, schizophrenia) r4
        • 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: r6
        • 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 r6
        • 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 r6
      • Maintain high awareness for potential complications such as development of pneumonia and sepsis r6
      • Physical restraints may be temporarily required; however, take care to avoid prolonged physical restraints without appropriate sedation owing to increased risk for rhabdomyolysis r2r16
      • Intermittent verbal reorientation to time, place, and date are important after stabilization r5
  • 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 r4r5
      • More than 200 mg diazepam or 40 mg lorazepam within 3 hours of treatment r4
    • If rapid escalation of benzodiazepines fails to control symptoms, adjunct treatment options include phenobarbital, propofol, ketamine, and dexmedetomidine r4
      • Dexmedetomidine and ketamine use has not been studied as much as phenobarbital and propofol use r4
      • Antipsychotic agents may be used as an adjunct to benzodiazepines; not recommended as monotherapy r21
    • Consider alternative or concurrent diagnosis r18
    • Refractory withdrawal and delirium tremens may require intubation and mechanical ventilation r4
    • Most experts do not recommend treating with ethanolr18 or baclofen (selective GABA-B receptor agonist) r4r21r54
  • Treat concurrent acute illness and comorbid conditions in standard manner
    • May include treatment of other pathologic processes leading to alcohol withdrawal such as: r4
      • 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,r4 β-blockers, and α₂-adrenergic agonists r12
    • Benzodiazepines
      • Choice of specific benzodiazepine
        • Long-acting benzodiazepines (eg, diazepam, chlordiazepoxide) are preferred in most patients r12
        • Intermediate-acting benzodiazepines (eg, lorazepam, oxazepam) are also effective and preferred in patients with liver dysfunction owing to lack of active metabolites r12
        • Chlordiazepoxide and oxazepam have less misuse potential than diazepam and lorazepam and may be preferred in patients at high risk for substance use disorders r12
      • Stress importance of abstinence from alcohol intake during treatment with benzodiazepine r12
        • 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 r12
          • Administration of dose during symptom-triggered management should be given for: r12
            • 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 r12
      • 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 r12
        • Symptoms usually resolve by day 7 following last alcohol use r12
    • Anticonvulsants
      • Data are limited;r55carbamazepine, valproic acid, and gabapentin may be used to reduce craving and prevent early relapser12
      • Anticonvulsants do not prevent withdrawal seizures or delirium tremens r12
    • β-blockers and α₂-adrenergic agonists
      • Atenolol and clonidine may be used as adjunct medications in combination with benzodiazepines to reduce adrenergic symptoms r12
      • 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) r6
  • ASAM placement criteria can guide placement after detoxification process r18r56
  • Provide patient with resources for assistance in long-term abstinence such as:
    • Alcoholics Anonymous r57
    • National Council on Alcoholism and Drug Dependence (local affiliates)
    • National Institute on Alcohol Abuse and Alcoholism r58
    • Substance Abuse and Mental Health Services Administration r59r60

Drug therapy

  • Benzodiazepines r2
    • Diazepam c132
      • Rapid onset of action allows for ease of titration with less risk of dose stacking than with lorazepam r4
      • Active metabolites result in a longer duration of action compared with lorazepam r4
      • Readminister drug in an escalating dose fashion every 5 to 10 minutes until sedation goals and normalized vital signs are achieved r4
        • Common escalating dosing pattern for diazepam: r4
          • 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 r4
      • 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 r12
        • 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 c133
      • 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 r4
      • 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 r4
        • Common escalating dosing pattern: r4
          • 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. r61
      • Example of outpatient oral lorazepam dosing regimens r12
        • 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 c134
      • 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 c135
      • 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 c136
      • 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 r12
        • 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 r52r62
    • Phenobarbital r63c137
      • Effective when used in combination with benzodiazepines for resistant withdrawal and delirium tremens r4
      • Paucity of data exists for use as monotherapy; therefore, monotherapy should only be considered in a patient whose condition is refractory to benzodiazepines r5
      • 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. Maximum cumulative dose of 1300 mg. r4r61
      • Infusion
        • Phenobarbital Sodium Solution for injection; Adults: 10 mg/kg IV infusion over 30 minutes. r4
          • NOTE: Not readily titratable due to delayed peak onset of action
  • Propofol r64r65c138c139
    • Reserved for severe withdrawal refractory to benzodiazepine therapy in patients requiring intubation and mechanical ventilation r5
    • 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. r66
  • α₂ receptor agonists
    • May reduce autonomic signs and symptoms of alcohol withdrawal as an adjunct therapy without an increase in benzodiazepine cumulative doses r67r68r69
    • Clonidine r12c140
      • 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 r70c141
      • Clinical effects include sedation, anxiolysis, analgesia, and sympatholysis; incidence of respiratory depression is lower compared with other adjunct agents available for severe, refractory withdrawal r5
      • Adjunct treatment may lower benzodiazepine requirements and decrease need for mechanical ventilation in patients with severe, refractory withdrawal r5
      • Does not prevent or treat withdrawal seizures and may increase rate of delirium, although available data are conflicting r5
      • 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). r4
  • β-blockers
    • Atenolol c142
      • 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 r12
          • Pulse 80 beats per minute or higher: 100 mg typical dose r12
  • Ketamine c143
    • Very limited data demonstrate safety when used as an adjunctive therapy for benzodiazepine-resistant withdrawal; may reduce benzodiazepine dose requirements r5r47r61
      • 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. Dose titration to desired effect may be necessary. Doses up to 1.6 mg/kg/hour have been used. r61r71
  • Anticonvulsants
    • May be a beneficial adjunct in mild withdrawal states to diminish craving in outpatient setting r72
    • Carbamazepine c144
      • 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. r73r74
    • Valproic acid c145
      • 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. r12r75
    • Gabapentin r12c146
      • Conflicting evidence regarding whether adjunctive use reduces benzodiazepine dose requirements r76r77
      • Misuse has been reported and caution should be taken especially in patients with substance use disorder r78r79
      • Gabapentin Oral capsule; Adults: 1200 mg PO loading dose once, then 800 mg PO every 8 hours for 4 days, then 600 mg PO every 8 hours for 2 days, then 300 mg PO every 8 hours for two days. r80
  • Thiamine (vitamin B₁) r16
    • Prophylactic dose c147
      • Vitamin B₁ (Thiamine Hydrochloride) Oral tablet; Adults: 100 mg PO once daily for 3 to 5 days. r46
      • Vitamin B₁ (Thiamine Hydrochloride) Solution for injection; Adults: 100 mg IV once daily for 3 to 5 days. r4r5
    • Treatment dose for Wernicke encephalopathy c148
      • Thiamine should be given before any glucose administration to avoid precipitating Wernicke encephalopathy;r5several dosing regimens are available r81
      • 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. r4r11r25r82
  • Folate supplementation c149
    • Folic Acid Oral tablet; Adults: 1 mg PO once daily for 3 to 5 days. r4
    • Folic Acid Solution for injection; Adults: 1 mg IV once daily for 3 to 5 days. r4
  • 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 applicabler66
    Route of doseOralIntravenous, intramuscular, oral, rectalIntravenous, intramuscular, oralIntravenous, intramuscular, oralIntravenous, intramuscular, oral, rectalIntravenous
    Infusion dosingNot applicableNot applicable1 to 4 mg/hour†r611 to 20 mg/hour, titrate up to effect§10 mg/kg intravenous over 30 minutes**r40.3 to 6 mg/kg/hour as needed for appropriate sedationr66
    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 c150c151

  • Electrolyte abnormalities are common in patients with long-term alcohol use and those with severe withdrawal; correct in standard manner when indicated r27
    • 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 r4
    • Hypomagnesemia and hypophosphatemia may occur; usually result from dietary deficiency
      • Routine supplementation is not recommended r5
      • 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 r4

Fluids c152c153

  • 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 r2

Nutrition r6

  • Thiamine d7
    • Thiamine is a critical cofactor in carbohydrate metabolism; deficiency results in decreased glucose utilization r4
    • Thiamine deficiency is often present and increases risk of Wernicke encephalopathy (eg, altered mental status, ophthalmoplegia, ataxia) r4
    • Administer prophylactic dose for presumed thiamine deficiency to all patients presenting in withdrawal r4r16
    • Administer treatment dose to any patients with concerning manifestations for Wernicke encephalopathy r4
    • Administer thiamine before (preferred) or with glucose administration r5
  • Folate
    • Supplementation is recommended owing to low dietary folate intake, which may lead to megaloblastic anemia in patients with long-term alcohol use disorder r4
    • Multivitamins containing daily recommended allowance of folic acid are often used r5
  • Provide nutritional support to those with long-term alcohol use to prevent and/or treat ketoacidosis
    • Route of administration is individualized r6
      • Enteral is preferred (oral, nasogastric, or nasoduodenal) c154c155
      • Parenteral may be required c156
  • Glucose c157
    • Some patients may require glucose supplementation for hypoglycemia because of increased metabolic requirements in the setting of diminished glycogen stores r2
    • 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
c158

Comorbidities

  • Liver failure c159
    • 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 r2r4
    • Duration of any benzodiazepines may be significantly prolonged in patients with hepatic dysfunction; dose adjustment may be required r4
  • Renal insufficiency c160
    • Most benzodiazepines and their metabolites are eliminated by the kidney; dose adjustment may be necessary, particularly in agents with active metabolites r27
  • Wernicke encephalopathy c161
    • Administer treatment dose of thiamine for duration of 3 to 5 days to any patients with concerning manifestations for Wernicke encephalopathy r4r11
    • Administer thiamine before (preferred) or with glucose administration to avoid precipitating Wernicke encephalopathy in patients at risk r5r11

Special populations

  • Pregnant women
    • There are no structured guidelines or high-level studies regarding optimal treatment of alcohol withdrawal in pregnancy r83
    • As maternal health is vitally important to fetal health, benzodiazepines should still be considered first line treatment; barbiturates are also considered safe r21
    • 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 r6c162c163c164c165c166c167
      • 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 r4
        • Scoring evaluations may be spaced to hourly once treatment goals are reached r4
    • Maintain awareness and assess for other coexistent conditions and alternate medical causes for patient decompensation other than worsening or recalcitrant withdrawal r4
    • Monitor for adequacy of airway protection, frequent vital signs, and hydration status r5c168c169c170
  • Outpatient monitoring for patients requiring treatment
    • Guide monitoring type and frequency based on symptom severity and characteristics of individual patient and environment r12
    • Daily reassessments are required in most patients until symptoms abate, including: r12
      • Measurement of vital signs c171
      • Random alcohol breath analysis c172
      • Withdrawal symptom severity scale assessment (eg, Short Alcohol Withdrawal Score, Clinical Institute Withdrawal Assessment for Alcohol [Revised]) c173
    • 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 r12c174
    • 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 r12c175c176c177
  • Refer to regional protocols to guide monitoring strategy r25

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 syndromer9) r11c178c179c180c181c182
  • 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 c185c186c187c188
  • Wernicke encephalopathy c189d7
    • Alcohol use disorder may result in chronic thiamine deficiency characterized by cell damage to the mammillary body, thalamus, and hippocampus r16
      • May lead to the permanent amnestic syndrome or Korsakoff encephalopathy
    • Prevalence may be as high as 3% r9
    • Classically presents with confusion, ataxia, and ophthalmoplegia r16
    • Glucose administration without thiamine replacement can precipitate syndrome in patients with thiamine deficiency r16
    • Diagnosis may be missed if nystagmus and ataxia are not appreciated; mental status changes may be attributed to delirium tremens r9

Prognosis

  • Overall prognosis is best among patients without other acute medical problems r6
  • Morbidity and mortality are increased among patients with comorbidity, concurrent disease related to alcohol use disorder that complicates management,r6 and older ager7
    • 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% r4
  • 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 r5
  • Clinical course
    • Symptoms of acute withdrawal usually improve markedly by several days after abstinence r1
    • Persistent symptoms (eg, anxiety, insomnia, autonomic dysfunction) may occur in some patients for up to 6 months r1
      • 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 r84
    • About one-third of patients who develop seizures will progress to delirium tremens without treatment r4
    • Average length of hospitalization for acute withdrawal
      • General inpatients: about 5.4 days r6
      • ICU patients: about 12.5 days r6
    • Patients who develop delirium
      • Delirium usually subsides within a few days; rarely persists for up to 2 weeks r6
      • Return to baseline mental status may require several weeks for some patients r6
    • Long-term abstinence from alcohol among patients with alcohol use disorder r12
      • 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 r85

Screening and Prevention

Screening

At-risk populations

  • Hospitalized and patients with active alcohol use disorder d10

Screening tests

  • Universal screening of all hospitalized patients for at-risk or heavy drinking identifies patients who are at risk of experiencing alcohol withdrawal r21r24
    • Use formal assessment tools such as Alcohol Use Disorders Identification Test or Clinical Institute Withdrawal Assessment of Alcohol Scale
    • Consider measurement of blood alcohol concentration

Prevention r86

  • Treat hospitalized patients considered at risk for severe alcohol withdrawal with prophylactic benzodiazepines before the onset of symptoms r87
    • Also give thiamine supplementation to malnourished patients with alcohol dependency
  • 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 r12c193
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