EtOH Withdrawal

Arnold Tsai, M.D.

LAC-USC

September 10, 2019

OBJECTIVES

1. Identify, assess and diagnose patients in EtOH withdraw

2. Manage pts with AWS

3. Utilize different modalities to treat pts in AWS

BACKGROUND

• Alcohol is consumed by 80% of population at some time

• Low dose can beneficial effects

• Decrease rates of MI, CVA, dementia

• 35% drinkers experience anterograde amnesia

• regular binge drinking in the long-term is thought to be more likely to result in brain damage than chronic (daily) alcoholism

TYPES OF ETOH

TYPES OF ETOH (2)

BEER

MALT LIQUOR

TERMS FOR HARD LIQUOR

EFFECTS OF ETOH

• CNS Depressant

• Enhances inhibitory tone

• Modulates GABA activity

• γ-aminobutyric acid

• Major inhibitory neurotransmitter

• EtOH binds to GABA receptors

• Cross tolerance with benzo and barbiturates

EFFECTS OF BAL IN ABSENCE OF TOLERANCE

• BAL 80mg/dL = 0.08%

Blood Level, mg/dL Usual Effects

20 Decrease inhibitions, a slight feeling of intoxication

80 Decrease in complex cognitive functions and motor performance

200 Obvious slurred speech, motor incoordination, irritability and poor judgement

300 Light coma and depressed vital signs

400 death

DEFINITION

• Alcohol Withdraw Syndrome (AWS)• A progression of signs & symptoms that occur following the reduction or cessation of alcohol

intake after heavy and prolonged use

• Kindling effect• neurological condition which results from repeated withdrawal episodes

• Each withdrawal leads to more severe withdrawal symptoms than in previous episodes

• DSM-5 diagnosis • requires h/o reduction or cessation of heavy & prolonged alcohol use• w/in a few hrs - few days after alcohol reduction/cessation & clinically significant

distress or impairment

• 2 or more• autonomic hyperactivity (sweating or tachycardia > 100 beats/minute), increased

hand tremor, insomnia, n/v, transient hallucinations (visual, tactile, or auditory) or illusions, psychomotor agitation, anxiety, generalized tonic-clonic seizures

ALCOHOL WITHDRAW SYNDROME

• After repeated exposure to brain any sudden decrease will produce withdraw symptoms

• Caused

• Self discontinuation

• Incarceration

• Hospitalization

• 4 stages

• Elderly pts are at risk for more rapidly severe AWS

• Symptoms of alcohol withdrawal have been described at least as early as 400 BC by Hippocrates

• become a widespread problem until the 1700

• In the Western world about 15% of people have problems with Alcoholism at some point in time

STAGES

1. Minor Symptoms: 6-12 hrs

2. Alcoholic Hallucinosis:12-24 hrs

3. Withdrawal Seizures: 24-48 hrs

4. Delirium Tremens (DT): 3-7 days can occur up to 14 days

MINOR SYMPTOMS

• Outpt setting

• Alcohol screening

• AUDIT

• CAGE

• Plan to modify drinking behavior

• Frequent contact with clinician

ALCOHOL HALLUCINOSIS

• Alcoholic induced psychotic disorder

• DSM5

• usually visual hallucinations but sometimes Auditory tactile can present

• Likely caused by the presence of dopamine in limbic system with the possibility of other systems

• Sudden onset 12-24 hrs resolved 24-48

• Normal vitals, no global clouding of sensorium

• Better prognosis than DT

• Tx: BNZ & Neuroleptics

WITHDRAW SEIZURES

• Tonic clonic convulsions

• 12-48 hr after last drink

• Onset 4th -5th decade of life

• Singular or brief

• Not prolong or status

• If left untreated can progress to DT

DELERIUM

• Mental Confusion

• Agitation

• Fluctuating levels of consciousness

• Increase in BP

• Taychcardia

• Increase in respiration

TREMENS

DELIRIUM TREMENS

Definition: • Delirium associated with tremor and autonomic overactivity• Potential life-threatening complication of AWS• setting of acute reduction or abstinence from alcohol.• mortality rate of up to 5 percent• substantially higher chance of mortality if the condition goes untreated

HISTORY

• assess pattern of alcohol use

• time since reduction or cessation of alcohol and symptom onset

• estimated quantity and frequency of consumption

• kind of drink typically consumed

• drinking pattern (such as daily, weekly, or early in the day)

• previous episodes of alcohol withdrawal

SEVERE AWS

• Associated with fluid and electrolyte abnormalities

• Hypovolemic

• Hypokalemia

• Hypophosphatemia

• Hypomagnesemia

• Malnourished

INPT TREATMENTS

1. Perform history and physical 1. Liver dysfunction

2. GIB

3. Arrythmias

4. Glucose/electrolyte imbalance

2. Nutritional support• Malnourished, high metabolic needs

1. FA 1 mg qd

2. Thiamine 100mg qd

3. Mg (decreased in EtOH)

4. “Banana” Bag- thiamine, folate, a MV in isotonic saline with 5% dextrose/ MgS 3gm

3. CNS depressant

TREATMENT MODALITIES

• Benzodiazepines

• Anticonvulsants

• carbamazepine, oxcarbazepine, and divalproex may be useful in the treatment of alcohol dependence by reducing alcohol craving and in treating AWS through its anti-kindling effect

• did not prevent DTs or seizures

• Gabapentin

• Barbiturates

• Phenobarbital 130 – 260mg IV Q15 mins

• Reserved for refractory DT

• Propofol

• Refractory DT

ADJUNCT THERAPIES

• Less studied drugs used in treatment of AWS

• Baclofen

• Unproven, selective agonist of GABA-B receptor (not used for severe AWS)

• Antipsychotics

• Treat for agitations, confusion but may lower risk of seizures, may also reduce the severity of some withdrawal effects

• QT prolongations, lower seizure threshold,

• Beta blockers

• Propranolol

• Reduce minor symptoms of withdrawl, do not prevent seizures or DT

• Central Alpha-2 agonist

• Clonidine

• Reduces some symptoms of AWS

• Ethanol

• Difficult to titrated

CLINICAL PRACTICE

• First line Benzodiazpeines

• Highest margin of safetly, lowest cost

• reduce the symptoms of withdrawal including seizures and help to prevent symptom progression

• no strong evidence that any one bnz is superior in treating AWS.

• long-acting benzodiazepines may provide for a smoother withdrawal effect than the intermediate.

• Pt’s with reduced hepatic function, intermediate-acting agents may be safer

• do not have active metabolites.

TYPES OF BNZ

• Diazepam (Valium)

• LA with active metabolites

• 5-10mg dosing

• IV/PO

• Librium (Chlordiazepoxide)

• Long half life with active metabolites

• May lead to oversedation in pt with severe liver disease

• PO formulation only

• Lorazepam (Ativan)

• short half life with no active metabolites

• Advance liver cirrhosis, acute alcoholic hepatitis

• Reduced prolong effected to reduce oversedation

• PO/IV formulation, 1-4 mg dosing

TREATMENT SCHEDULING

• Example of fixed schedule and symptom triggered schedule

•*Studies have shown the symptom-triggered regimen can reduce medication use and shorten the duration of treatment

CIWA-AR

• Clinical Institute Withdrawal Assessment for Alcohol–Revised

• Score Withdrawal Level

• ≤8 Absent or minimal withdrawal

• 9-19 Mild to moderate withdrawal

• ≥20 Severe withdrawal

CIWA-AR GUIDED TREATMENT

• Treatment begins with CIWA-Ar scores 8-10• Rarely needs pharmacologic treatment

• Scores of 10-20• pharmacologic treatment is indicated but clinical judgement

• If > 20 transfer to MICU?

• req. formal assessing pt 10-15 mins for pt with severe symptoms• 4-6 hrs reasonable for stable pt with mild symptoms• Severe symptoms• Diazepam 5-10mg Q5-10 mins

• Ativan 2-4mg Q15-20 mins

• Goal: sedation but pt should be alert

• If pt greater risk of adverse outcomes needs heavier sedation

OTHER TREATMENTS

• Anticonvulsants

• Carabamizpine*

• carbamazepine was found to be safe and tolerable when administered at daily doses of 800 mg (fixed or tapered over 5–9 days)

• associated with a significant reduction in alcohol withdrawal symptoms as measured by CIWA-Ar

• underpowered to assess carbamazepine's role in reduction of seizures and DTs

• Valproic Acid*

• increase GABAergic tone and efficacy as a mood stabilizer

• Reduction of AWS symptoms, AWS seizures and AWS delirium

• underpowered to examine seizures and DTs as outcomes

• Divalproex sodium*

• 500 mg 3 times per day

• safe detoxification,

• divalproex alone reduced irritability

• reduction in AWS symptoms, AW seizures, AW delirium,

OTHER TREATMENTS (2)

• Gabapentin*

• reduction in observer-rated AWS symptoms

• effective pharmacotherapy in the treatment of mild-to-moderate but not severe AWS symptoms

• Dose of 400mg TID (1200mg) Day 1-3 with day 4 taper to 400mg BID

• Lower odds of drinking during and even after completing of treatment compared to BNZ

• Less anxiety

• Less cravings

• Less daytime sedation

• Not metabolized in Liver, does not induce Liver enzyme, renal excreted

• Moderate side effect profile

OTHER TREATMENTS (3)

• Pregabalin

• dosing between 200 and 450 mg/day

• reduction in CIWA-Ar scores and alcohol craving

• pregabalin demonstrating significantly better treatment for ‘headache’ and ‘orientation’ withdrawal symptoms

• Levetiracetam

• fixed dose starting at 2000 mg/day tapered over 6 days

• Not much difference in results as

• Topiramate was initiated at a daily dose of 25 mg

• Topiramate 25 mg fixed dose every 6 h (100 mg/day) over 7 days

• reducing alcohol craving, as well as symptoms of depression and anxiety

• No reduction of AWS

OTHER TREATMENTS (4)

• Zonisamide

• dose range of 400–600 mg/day and tapered over the remaining 3 weeks to 100–300 mg/day.

• zonisamide group had lower CIWA-Ar, craving, and anxiety scores than the diazepam group. While promising, there are insufficient data to support the use of topiramate or zonisamide for the treatment of AWS at this time.

• Conclusion:• More controlled clinical trials are needed to measure the efficacy of

nonbenzodiazepines in the treatment of AWS and AUD.

QUESTIONS

RE-CAP

• Benzo, Benzo, Benzo is treatment of choice

• 3 different benzodiazepines frequently used

• Symptom-triggered therapy

• Frequent reassessment of pts

• If pt continues to use >50mg of Diazepam or >10mg lorazepam in first hour consider ICU

• Other modalities

• Cabamazepine 800 QD

• Gabapentin 1200mg QD