Alcohol withdrawal management

management of complicated alcohol withdrawal

1. MANAGEMENT OF COMPLICATED ALCOHOL WITHDRAWAL Ravikant Kumar

2. Overview Introduction Alcohol Withdrawal Seizures Alcoholic Hallucinosis Delirium Tremens Wernicke’s Encephalopathy

3. INTRODUCTION 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. pathogenesis of alcohol withdrawal syndrome Carlson et al. Crit Care Clin 2012

5. Time course in AWS

6. 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

7. Admission studies 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

8. Connor et al. Lancet 2016

9. 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

10. WITHDRAWAL SEIZURES

11. Seizures in alcohol dependence 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 ( N’Gouemo et al. 2015)

13. epilepsy vs alcohol withdrawal seizures Epilepsy Early alcohol withdrawal Consciousness level Post-ictal sleep/ drowsiness Sleeplessness Mood Calm Anxiety, unrest, nightmares Tremor or Sweating No Yes Blood pressure Normal Elevated Pulse rate Normal Elevated (>90) Temperature Normal/light fever Fever Arterial blood Normal Respiratory alkalosis a EEG Pathology b Normal, low amplitude Questionnaires Normal scores Normal or elevated scores a Respiratory alkalosis may be masked by seizure-induced metabolic acidosis, but it will reappear within 2 h after cessation of convulsions ( Orringer et al., 1977) b Initial post-ictal slowing in most patients. Inter-ictal epileptiform discharges in approx. 50% (FIRST Group, 1993). EFNS Guideline. European Journal of Neurology 2005

14. Withdrawal seizures: prevention 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. Withdrawal seizures: management 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. Withdrawal seizures: management 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 et al. 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. Hallucinosis

18. 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. Miller. Interventions For Addiction 2013

19. Alcoholic Hallucinosis 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 Miller. Interventions For Addiction 2013

20. Alcoholic Hallucinosis : Management 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 NSW drug and alcohol withdrawal clinical practice guidelines. 2007 The Maudsley prescribing guidelines in psychiatry. 2015

21. DELIRIUM TREMENS (DT)

22. 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% Connor et al. Lancet 2016 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. ICU delirium versus alcohol-withdrawal delirium tremens Features ICU Delirium Delirium Tremens Predominate subtype Mixed or hypoactive Hyperactive Associated critical illness or respiratory failure Usually Sometimes Prognosis Adverse Good Morbidity/mortality Adverse a/w presence of delirium Related to comorbid conditions Duration Variable; may progress to dementia Days Recurrence Not expected May have several Episodes of AWS or delirium tremens; ? kindling Pathogenesis Multifactorial ? Cholinergic ? Tryptophan Multifactorial: GABA, NMDA, etc. Management ? Dexmedetomidine , Avoid BZDs Multiple agents, especially BZDs

25. 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 Schuckit , N Engl J Med. 2014

26. 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

27. Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) Wesley et al. JAMA. 2001

28. Sessler et al. Am J Resp Crit Care Med 2002

29. DT: Management 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

30. Medications Benzodiazepines are treatment of choice Oral loading dose of diazepam/ lorazepam 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 “The practitioner should not hesitate to use whatever amounts are needed to control the agitation” ASAM Principles of addiction medicine

31. Diazepam regimens Lorazepam regimens Regimen 1 10–20 mg IV or PO every 1–4 hr , as needed 8 mg IV/IM/PO 15 min Repeat 8-mg bolus IV 10–30 mg/ hr Regimen 2 5 mg IV (2.5 mg/min) If needed 10 min later repeat If needed 10 min later 10 mg IV If needed 10 min later 20 mg IV If needed 10 min later 20 mg IV Continue to administer 5–20 mg/ hr , as needed. 1 to 4 mg IV every 5–15 min or 1–40 mg IM every 30–60 min Continue dosing every hr as needed to maintain somnolence

32. Medications 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

33. 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 a All methods are associated with substantial risk of respiratory failure. Carlson et al. Crit Care Clin 2012

34. WERNICKE’S ENCEPHALOPATHY

35. 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’

36. WE 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

37. We : clinical features 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 EFNS guidelines. European Journal of Neurology 2010 Latt & Dore. Internal Medicine Journal 2014

38. We : management 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

39. prophylactic thiamine Offer to harmful or dependent drinkers: if they are malnourished or at risk of malnourishmentor if they have decompensated liver disease or if they are in acute withdrawal or before and during a planned medically assisted alcohol withdrawal NICE. 2010

40. Thiamine Thiamine Treatment of patients with a definitive diagnosis of WE 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 Prophylactic treatment of suspected or at risk patients 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) Latt and Dore. Internal Medicine Journal (2014)

41. Thank you