ALCOHOL WITHDRAWAL SYNDROME. Dr. LANDO ELVIS.pptx

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

5. TIME COURSE IN AWS

6. 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)

7. 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

8. 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

9. 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

10. 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

11. 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.

12. . 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

13. EPILEPSY vs ALCOHOL WITHDRAWAL SEIZURES

14. 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)

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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 .

26. 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

27. 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

28. 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

29. 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

30. 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 )

31. 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.

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