Alcohol Withdrawal Syndromes AMU Nurse Study Day Tom Heaps Consultant Acute Physician

Lesson Plan Alcohol Withdrawal Syndromes Introduction and Pathophysiology Clinical Cases Complications Management HEFT Clinical Guidelines for Alcohol Withdrawal Summary

Alcohol - a growing problem 55% of men and 53% of women drink > recommended daily amounts (31% of men and 24% of women drink >2x recommended daily amounts) 1,008,850 NHS hospital admissions related to alcohol in 2012/13 (double the number of alcohol-related admissions in 2003) 30,460 NHS admissions for alcohol intoxication or withdrawal in 2012 6,490 deaths related to alcohol in 2012 cost to NHS in 2012/13 £3.5billion Statistics on Alcohol in England 2014 www.hscic.gov.uk

Pathophysiology of AWS Stimulating Neurotransmitters Depressing NMDA and Glutamate GABA

Balance with chronic alcohol intake Excitatory Neurotransmission Inhibitory Neurotransmission  NMDA and Glutamate GABA Alcohol

Sudden cessation of alcohol intake… Excitatory Neurotransmitter Excess Inhibitory Neurotransmission NMDA and Glutamate GABA Alcohol

Kindling increasing severity of withdrawal after repeated withdrawal episodes increasing risk of withdrawal seizures with increasing number of previous withdrawal episodes progressive brain damage by excitatory neurotransmitters with each withdrawal episode may lead to permanent cognitive impairment (dementia) prompt benzodiazepines (and certain anti-epileptic drugs?) may protect against this

Clinical Case 1 67-year-old male with 40y Hx of alcohol excess presents 1d after stopping drinking seeing insects ‘scurrying about everywhere’ and feels them crawling over his skin calm, not drowsy or confused, no overt Sx of withdrawal not sweating, normal HR and BP DIAGNOSIS?

Alcoholic Hallucinosis NOT the same thing as alcohol withdrawal or delirium tremens (DTs) develops within 12-24h of abstinence and resolves after 24-48h visual hallucinations +/- auditory and tactile NOT associated with confusion or altered conscious level NOT usually associated with tachycardia, hypertension, sweating etc. no specific Rx required unless symptoms of withdrawal develop

Clinical Case 2 WITHDRAWAL SEIZURE OR SOMETHING ELSE? 57-year-old female, drinking 4l of vodka every week for 6/12 still drinking but ‘trying to cut down’ presents to ED following a generalized tonic-clonic seizure further seizure in ED 4h after first, terminated spontaneously 2m drowsy for several hours, transferred to AMU, started on CDZ, bloods NAD 6h after transfer complains of focal twitching affecting left arm subsequent seizure terminated after 7min with IV diazepam 10mg WITHDRAWAL SEIZURE OR SOMETHING ELSE?

Alcohol-related seizures 1 12-48h of abstinence (may also occur with alcohol intoxication) may occur as soon as 2h after stopping drinking may also occur after just cutting down alcohol intake brief generalized tonic-clonic with short post-ictal phase may be single or multiple (60%) occurring over a short time period <6h status epilepticus is rare occurring in <3%

Alcohol-related seizures 2 prolonged/recurrent seizures evidence of head injury focal onset or lateralizing neurology fever/meningism prolonged post-ictal drowsiness check CBG in ALL cases and institute usual nursing care / monitoring additional investigations e.g. CT scan, LP (for cause other than ETOH) if any red flags: Rx with ADEQUATE doses of benzodiazepines +/- phenobarbital (phenytoin usually ineffective) inadequate Rx increases risk of DTs by 30-40%

Alcohol Withdrawal Syndrome (AWS) Decreased brain inhibition (GABA) Increased brain stimulation (glutamate, NMDA, cortisol, adrenaline, noradrenaline, dopamine) onset typically 6-36h after cessation with resolution within 48-96h like seizures, may occur after just reducing alcohol intake (and with significant blood alcohol concentrations still present) anxiety, agitation, insomnia tremulousness nausea, anorexia, vomiting, diarrhoea headache, diaphoresis, palpitations tachycardia, hypertension

Clinical Case 3 39-year-old male alcoholic ‘successful’ withdrawal in community by GP brought to ED by sister 10d after stopping drinking ‘can’t cope with him anymore’ increasing paranoia ‘the gypsies are out to get me’ not sweating/tremulous/tachycardic BP 160/102, bloods/CT NAD admitted to AMU witnessed ‘plucking’ at imaginary objects on the floor and having conversations with himself drowsy at times and agitated/aggressive/wandering at others DIAGNOSIS?

Delirium Tremens (DTs) occurs in 5% of alcohol withdrawal onset usually 48-96h after cessation (delayed onset up to 2w reported) duration usually 1-5d (up to 4w reported) significant confusion, disorientation and severe anxiety, fear, paranoia agitation, restlessness, insomnia or prolonged periods of sleeping hallucinations primarily visual (insects, rats, tiny people, ‘pink elephants’) tactile (crawling sensations - formication) auditory (threatening, persecutory) autonomic symptoms i.e. tachycardia, fever, hypertension, sweating (sometimes not prominent) Delirium tremens

What are the risk factors for DTs? prolonged history of sustained drinking prior to withdrawal significant withdrawal symptoms in the presence of elevated blood alcohol previous episodes of DTs older age (uncommon <30) and male sex concurrent illness e.g. infection longer delay from stopping drinking to presenting with symptoms of withdrawal and inadequate Rx for alcohol withdrawal / seizures

What complications is he at risk of? dehydration (sweating, vomiting, diarrhoea, fever) low potassium, magnesium and phosphate (D&V, renal losses) seizures arrhythmias (electrolytes and stress hormones) infection especially pneumonia Wernicke's encephalopathy: thiamine (vitamin B1) deficiency confusion, abnormal eye movements and unsteadiness (ataxia) may lead to Korsakoff’s dementia if untreated mortality 5% (previously 20-40%)

How should he be initially assessed? Diagnosis of withdrawal and DTs is clinical Rule out alternative diagnoses (especially in DTs) infection e.g. meningoencephalitis, pneumonia metabolic disturbance trauma e.g. SDH, fractures hepatic encephalopathy, GI haemorrhage drug toxicity/overdose Investigations FBC, U&E, LFT, amylase, CRP, INR, G&S, Ca2+, Mg2+, PO43-, glucose, alcohol ECG, CXR, blood cultures, urinalysis (CT +/- LP)

Management of AWS: the essentials IV fluid to maintain hydration replace electrolytes (potassium, magnesium, phosphate) IV thiamine (Pabrinex®) and PO multivitamins nutritional supplements, IV glucose, NG feeding benzodiazepines for symptoms / prevention of seizures LMWH if immobile and no coagulopathy daily bloods U&E, magnesium, calcium, phosphate

Management of AWS: benzodiazepines PO chlordiazepoxide (10-30mg QDS plus PRN) often preferred due to long t1/2, gradual onset and low risk of over sedation PO diazepam (2-5mg QDS plus PRN) is an alternative with more rapid onset of action PO lorazepam (0.5-1mg QDS plus PRN) or oxazepam are preferred if significant liver disease IV diazepam or lorazepam may be used for seizures or acutely disturbed patients with DTs avoid IM route if possible due to unpredictable absorption

Symptom-triggered dosing regimens similar clinical outcomes to fixed-dosing with lower total benzodiazepine doses and shorter duration of treatment required median total chlordiazepoxide dose 100mg vs 425mg and median duration of therapy 9h vs 68h in one comparative study frequent (nurse-led) assessment of patients (initially every 10- 15min in severe withdrawal, 4-6h in mild withdrawal) required using CIWA-Ar or GMAWS scale further doses of benzodiazepines administered only if CIWA-Ar or GMAWS score above a certain value each time patient assessed achievable on a typical day on AMU?

Management of severe AWS/DTs often requires use of the Mental Capacity Act and a degree of physical restraint repeated boluses of IV diazepam (5-10mg) or IV lorazepam (2-4mg) until symptoms controlled (avoid IM as absorption erratic) subsequent high dose oral treatment e.g. chlordiazepoxide 50mg QDS or diazepam 10mg QDS PLUS PRN doses doses up to 1000mg diazepam over 24h sometimes required consider IV phenobarbital or propofol for benzodiazepine- refractory patients (intubation on ITU may be required)

Alcohol Withdrawal Guideline

Timing of Alcohol Withdrawal Syndromes

AWS: Summary very common cause of acute medical admission hallucinosis/seizures  AWS  delirium tremens important not to forget alternative diagnoses and THINK GLUCOSE IV fluids, Pabrinex (high-dose for most patients), nutritional supplements monitor and replace electrolytes (K+, Mg2+, PO43-, Ca2+) +/- cardiac monitor ADEQUATE doses of PO benzodiazepines (chlordiazepoxide or diazepam, lorazepam in liver failure) regularly AND PRN: use GMAWS if possible IV diazepam or lorazepam for seizures/severe agitation/DTs refer patients to CRI (formerly Aquarius) for outpatient support or community detox and RAID for advice / support regarding management

Questions