ALCOHOL WITHDRAWAL SYNDROME. Dr. LANDO ELVIS.

1. ALCOHOL WITHDRAWAL
SYNDROME
DR. LANDO ELVIS

2. OVERVIEW
• Introduction
• Assessment
• Pathophysiology
• Alcohol Withdrawal Seizures
• Alcoholic Hallucinosis
• Delirium Tremens
• Wernicke’s Encephalopathy

3. INTRODUCTION
• Alcohol withdrawal syndrome (AWS) can occur when an individual stops or
even significantly reduces alcoholic consumption after a prolonged period
of use.
• Alcohol withdrawal syndrome (AWS) usually mild – moderate in majority of
patients
• About 10% of patients have complications during AWS – complicated AWS
• Complicated AWS
Withdrawal seizures
Hallucinations
Delirium tremens
Wernicke encephalopathy

4. PATHOPHYSIOLOGY
• Two neurotransmitters in the brain are affected by chronic alcohol consumption and play a major role in AWS.
• Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter and glutamate is the primary excitatory
neurotransmitter
• Together these neurotransmitters maintain neurochemical balance in the brain
• The presence of alcohol inhibits the function of the N-methyl-d-aspartate (NMDA) receptor, leading to the sedative and
anxiolytic effects of alcohol as well as to impaired memory and the generation of potentially life-threatening seizures
• During withdrawal, GABA levels decrease below normal capacity, which ultimately leads to hyperactivity of the nervous
system
• At the same time, glutamate is activated, which in turn increases the function of the NMDA receptors
• A process known as kindling has been proposed to explain the decrease in time of onset and increase in severity of
symptoms in patients who have undergone repeated episodes of withdrawal
• This is related to the frequent changes in GABA and NMDA receptors as described above

7. TIME COURSE IN AWS

8. ASSESSMENT & DETERMINATION OF TREATMENT
GOALS
The initial evaluation of a patient with suspected alcohol use disorder include
assessment of current and past use of tobacco and alcohol as well as any misuse of other
substances, including prescribed or over-the-counter medications or supplements.
• Rationale:
• Establish baseline level and pattern of symptoms to assess later treatment response
• Develop a treatment plan to reduce symptoms, morbidity, and mortality
• Implementation:
• Obtain via face-to-face evaluation, review of medical records, and/or history (including from collateral
informants)

9. Assessment (continued)
• AUD Symptoms and Severity:
 Alcohol is often taken in larger amounts or over a longer period than was intended.
 There is a persistent desire or unsuccessful efforts to cut down or control alcohol use.
 A great deal of time is spent in activities to obtain alcohol, use alcohol, or recover from its use.
 Craving, or a strong desire or urge to use alcohol.
 Recurrent alcohol use resulting in a failure to fulfill major role obligations at work, school, or home.
 Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated
by the effects of alcohol.
 Important social, occupational, or recreational activities are given up or reduced because of alcohol use.
 Recurrent alcohol use in situations in which it is physically hazardous.
 Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that
is likely to have been caused or exacerbated by alcohol.
 Tolerance, as defined by either of the following:
 A need for markedly increased amounts of alcohol to achieve intoxication or desired effect.
 A markedly diminished effect with continued use of the same amount of alcohol.
 Withdrawal, as manifested by either of the following:
 The characteristic withdrawal syndrome for alcohol.
 Alcohol (or a closely related substance, such as a benzodiazepine) is taken to relive or avoid withdrawal
symptoms.
• Mild: presence of two-three symptoms
• Moderate: presence of four-five symptoms
• Severe: presence of six or more symptoms

10. RISK FACTORS
1. Prior episodes of AWS requiring detoxification, including seizures or
delirium (kindling)
2. Grade 2 severity or higher on presentation (CIWA-Ar Score >10)
3. Acute or chronic comorbid conditions, including alcoholic liver disease,
co-intoxications,trauma, infections, sepsis
4. Use of “eye opener,” high daily intake of alcohol, or number of drinking
days/month
5. Detectable blood alcohol level on admission
6. Abnormal liver function (serum aspartate aminotransferase activity >80
U/L)
7. Prior benzodiazepine use

11. ADMISSION INVESTIGATIONS
1. Complete blood cell count
2. Baseline metabolic panel with s. electrolytes (including magnesium), glucose,
renal function tests
3. Blood alcohol, and urine and blood toxicology studies
4. Serum calcium, phosphate, lipase, CPK activity
5. Liver function tests, including INR and serum AST, ALT, bilirubin, ammonia
6. Chest radiograph
7. Electrocardiogram, cardiac biomarkers, echocardiogram
8. Urinalysis
9. Arterial blood gas analysis
10. Blood, urine, and sputum cultures

13. POTENTIAL INDICATIONS FOR ICU MANAGEMENT
1. Advanced Stage 2 or greater alcohol withdrawal syndrome
2. Critical comorbid conditions
3. Escalating intravenous bolus or continuous-infusion sedation
therapy
4. Persistent fever >39 C

14. WITHDRAWAL SEIZURES
• Overall, 15% alcohol dependence patients experience seizures. (Hillbom et
al. CNS Drugs 2003)
• One third seizure-related admissions are related to WS (Brathen et al. EFNS
guideline 2005)
• Other causes of seizures in ADS:
Metabolic
Infectious
Trauma
Cerebrovascular conditions
Concomitant use of other substances, particularly benzodiazepines.

15. .
Risk factors:
• Heavy drinking and past history of WS
• 90% of WS occur within 48 hours of stopping alcohol use
• Grand mal type convulsions (tonic-clonic seizures)
• If focal type/partial seizures → rule out other causes
• No clear evidence for a genetic position to alcohol withdrawal
seizures

16. EPILEPSY vs ALCOHOL WITHDRAWAL SEIZURES

17. PREVENTION OF WITHDRAWAL SEIZURES
• Benzodiazepines are medications of choice in prevention of WS (Hillbom
et al. CNS Drugs 2003)
• Effective in preventing recurrence of WS
 Loading dose regimen of diazepam preferred
 Anticonvulsants are equally as efficacious as BZDs in seizure
prevention
• There is no advantage when combined (Lingford-Hughes et al. BAP Guidelines
2012)

18. MANAGEMENT OF WITHDRAWAL SEIZURES
• Patient should be managed in inpatient setting
• Investigations to rule out other causes of seizures
• Continuous monitoring
 Vital signs
 Alcohol withdrawal symptoms
 Recurrence of seizures
 Neurological symptoms

19. MANAGEMENT OF WITHDRAWAL
SEIZURES..cont
• Thiamine administration (100 mg t.i.d. i.m/i.v) before administration
of any carbohydrate (including glucose)
• Diazepam in loading dose should be initiated
• Nursing in calm environment
• Secondary prevention of seizures - phenytoin not effective (Hillbom etal.
CNS Drugs 2003)
• No role of anticonvulsants on long term basis (Hillbom et al. CNS Drugs 2003)
• Abstinence from alcohol is best way to prevent recurrence of WS

20. ALCOHOLIC HALLUCINOSIS
• Onset - 12 to 24 hours of abstinence
• Resolution - typically within 24 to 48 hours
• Hallucinations are visual (usually), auditory and tactile
• Visual hallucinations are most common and frequently involve some type
of animal life.
• Auditory hallucinations - unformed sounds (such as clicks or buzzing) or
formed voices.
• Tactile hallucinations may involve a sensation of bugs or insects crawling on
the skin.
• Patients are aware that they are hallucinating and often very distressed
• No global clouding of the sensorium but only with specific hallucinations
• Milder cases - sensorium is otherwise clear and the patient retains insight
• In more severe withdrawal, this insight may be lost

21. MANAGEMENT OF ALCOHOLIC HALLUCINOSIS
• Mild perceptual disturbances respond to benzodiazepines
• Oral haloperidol if higher severity
• IM/IV or (very rarely) if necessary
• Olanzapine - 5 mg to 10 mg orally or buccally

22. DELIRIUM TREMENS (DT)
• Referred to as alcohol withdrawal delirium
• Onset within 1 – 4 days after stopping alcohol (usually ~3 days)
• Lasts from 1 to 8 days or more (usually 2 or 3 days)
• Incidence of DT: ~5%
• DT can lead to death among ADS patients
• 30% mortality in earlier western studies
• 5% mortality currently in western studies due to improved management
• Hyperthermia, cardiac arrhythmias, complications of withdrawal seizures,
or concomitant medical disorders

23. DT: CLINICAL FEATURES
Long history of regular, heavy alcohol use Sudden stopping of alcohol. Onset within short
period of time, of the following:
Alcohol withdrawal
• tremors,
• anxiety,
• restlessness,
• insomnia,
• hypertension,
• fever)
Delirium
• Disturbance in consciousness: disoriented to
time, place and person(delirium)
• Perceptual disturbance
• Illusion: mistaking cracks in wall to snakes
• Hallucinations: seeing small objects/persons
(Lilliputian hallucinations)
• Agitation

24. DT RISK FACTORS
• CIWA-Ar scores > 15 (especially in a/w a systolic BP>150 mmHg or a pulse
rate >100 beats/minute)
• Recent withdrawal seizures (seen in 20% of persons with delirium)
• Prior withdrawal delirium or seizures
• Recent misuse of other depressant agents
• Concomitant medical problems - Electrolyte abnormalities (e.g., low levels of
potassium, magnesium, or both), low platelet counts, and respiratory,
cardiac, or GI disease

25. DT: MANAGEMENT
Care in an inpatient setting, preferably an intensive care unit
Thorough assessment
• H/O alcohol dependence
• Detailed systemic and neurological examination
• Rule out concomitant medical comorbid conditions: head injury, hypoglycemia,
metabolic disturbances, liver failure, pancreatitis, GI hemorrhage, meningitis, etc.
• Assessment tools: Confusion assessment method for the ICU (CAM-ICU)
/Intensive care delirium screening checklist (ICDSC)
• Investigations
• Blood sugar levels
• Serum electrolyte
• Liver function tests

26. DT: MANAGEMENT..cont
• Quiet well-lit surroundings with minimal stimuli
• Close monitoring of vital signs (e.g., every 15–30 min)
• A functioning intravenous line
• Administer IV thiamine at a dose of 500 mg once or twice a day for 3 days
• Ensuring adequate hydration & correction of electrolyte imbalance
• Medications to control agitation, promote sleep, and raise seizure threshold
• Control of agitation is most important and requires aggressive sedation
Benzodiazepines are treatment of choice
• Oral loading dose of diazepam (10–20 mg IV or PO every 1–4 hr, as needed) /lorazepam (8 mg IV/IM/PO 15 min—
max30mg/hr) till desired effect
• If rapid sedation required → intravenous diazepam
• No single drug of this class superior to another
• Goal is to sedate the patient to a point of light sleep or a calm but awake state

27. DT: MANAGEMENT..cont
Antipsychotics to be used only if agitation is not controlled by benzodiazepines
• Used as adjunct to BZD and not ‘instead of’ BZD
•Adjunctive haloperidol for uncontrolled agitation or hallucinations
 0.5–5.0 mg IV/IM every 30–60 min as needed— not to exceed 20 mg
or
0.5–5.0 mg orally every 4 hr up to 30 mg
•Newer antipsychotics (olanzapine, risperidone) have better safety profile
• Patients with DT have higher chance of further episodes in subsequent
withdrawals

28. Severely agitated delirious patients
1. Progressively larger IV bolus doses of benzodiazepines or barbiturates
2. Titrated IV infusion of benzodiazepines
3. Addition of IV rescue therapy to #1 or #2
a. Propofol
b. Dexmedetomidine
NB: All methods are associated with substantial risk of respiratory failure.

29. WERNICKE’S ENCEPHALOPATHY (WE)
• Acute neuropsychiatric resulting from acute deficiency of thiamine (vit B1) in chronic alcohol
users
• Poor dietary intake
• Intestinal malabsorption
• Reversible if treated early (within the first 48–72 h of the onset)
• Untreated cases can have irreversible damage called as ‘Korsakoff’s syndrome/psychosis’
• Prevalence from autopsy studies - 0.4% and 2.8%, Prevalence in patients with AUD -12.5%
• 25% of WE recover completely
• 25% do not recover and develop Korsakoff’s syndrome
• Chronic, disabling condition
• Severe anterograde amnesia: inability to learn new information
• Confabulation (filling up gaps in memory through imaginary stories)
• May require long term institutionalisation in some patients ~ 20%
• There is no effective treatment of korsakoff’s syndrome

30. CLINICAL FEATURES OF WE
• Classic triad: Reported only in 16-20% of patients with WE
 Acute onset of confusion (in 53%)
 Cerebellar signs (ataxia, in 25%)
 Eye signs: ophthalmoplegia, nystagmus (in 24%)
• May also result in hypothermia, hypotension, coma and death
• Contrast enhanced MRI: bilateral lesions in mammillary bodies

31. MANAGEMENT OF WE
• Usually underdiagnosed condition
• Suspicion should be high in all heavy drinkers presenting with coma,
memory impairment → positively rule out Wernicke’s encephalopathy
• Thiamine should be given before any carbohydrate administration
• Correct hypomagnesaemia and other electrolyte disturbance, if present
• If drinking persists →maintain on oral thiamine (100 mg/day) till abstinence

32. Prophylactic thiamine
• Offer to harmful or dependent drinkers:
if they are malnourished or at risk of malnourishment or
if they have decompensated liver disease or
if they are in acute withdrawal or
before and during a planned medically assisted alcohol withdrawal

33. THIAMINE
• Treatment of patients with a definitive
diagnosis of WE
• Prophylactic treatment of suspected or at
risk patients
• Depending on the state of malnutrition:
• At least 200–500 mg TDS IV for 5–7 days →
• Oral thiamine 100 mg TDS for 1–2 weeks →
• 100 mg daily thereafter
• At least 100–200 mg TDS IM/IV for 3–5 days
• →
• Oral thiamine 100 mg TDS for 1–2 weeks →
• 100 mg daily thereafter
• (I/M if I/V not possible )

34. CONCLUSION
• Risk factors and severity assessment
• Investigations
• Inpatient management and ICU management for very severe cases
• Because of the severity and complications that can arise from AWS, it is
important to be familiar with proper treatment.
• Administer IV thiamine at a proper dose.
• Thiamine administration (i.m/i.v) before administration of any
carbohydrate (including glucose)
• The use of benzodiazepines is beneficial in lessening agitation, preventing
withdrawal seizures, and reducing the progression of withdrawal
symptoms.

35. *END*
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